Category Archives: Embryology

Embryology

Precongress courses at ESHRE23 characterised by practicality and … – ESHRE

Nineteen PCCs have been scheduled for this years annual meeting, 13 organised by ESHREs Special Interest Groups covering a wide range of themes and presenting speakers of international renown. A record number of abstracts have been received for the main scientific programme.

As ever, this years PCCs are characterised by a strong thread of practicality and topicality, with presentations from experts of international acclaim. Two of the courses, from the SIG Embryology and SIG Implantation & Early Pregnancy, will complement publication of two imminent ESHRE guidelines, on add-ons in ART and on recurrent implantation failure. Both guidelines have completed their stakeholder review and will be featured specifically in the courses. Add-ons, of course, have been a hot topic for ESHRE for several years, giving rise to a far wider general discussion of how to introduce new developments into everyday practice. The latter is the theme of a dedicated course from the SIG Global & Socio-cultural Aspects of Infertility, which is likely to be provocative at least, with presentations from among others Sebastiaan Mastenbroek, Simon Fishel, Jack Wilkinson and Ben Mol. Wilkinsons presentation has a strong practical theme on a subject which seems more usually beset by opinion - on how to introduce new technologies responsibly. Claims and counter-claims present a minefield for patients (help, hype and hope), which Manuela Perrotta hopes to unravel in her presentation on informed consent.

The SIG Implantation & Early Pregnancy describes recurrent implantation failure as a unique riddle, subject to different perspectives and putative solutions. These different perspectives are largely represented in a wide-ranging course which covers male, female and embryonic factors in a condition which affects 10% of the IVF population. Susan Golombok, from the Centre for Family Research in Cambridge, whose work has done so much to underline the acceptability of the new family dynamics which ART has made possible, will consider alternative approaches to parenthood. The daily routine of managing RIF patients will be reviewed by Bettina Toth.

Time-lapse systems are now ubiquitous in the IVF lab, especially in Europe, and they too feature prominently in this years PCCs, either in the practicality of new introductions or as a routine luxury or necessity. The latter features in a programme of debates organised by the SIG Reproductive Endocrinology, which also includes the hot topics of freeze-all, cycle programming ahead of FET, PGT-A for embryo selection, duo-stim and managing the luteal phase.

Two courses of great topical interest feature the introduction and application of artificial intelligence in reproductive medicine. Presentations will start with the basics and further consider how AI might help in embryo selection for transfer and endometrial receptivity. Even more topical, with the imminent revision of the EUs tissue and cell directives into a single directive, is a course organised by the SIGs Ethics & Law and Psychology & Counselling on the varying regulations in Europe on third-party gamete donation. Enhanced protection of donors is likely to be a major component of the new directive, and this PCC will consider how regulation has an impact on the practice of third-party donation.

Despite the vein of practicality running through many of these courses (indeed, the session on AI is sub-headed a practical course for IVF practitioners), basic science also figures prominently in sessions organised by the SIGs Andrology, Reproductive Genetics and Stem Cells. The theme for the course devised by the SIG Stem Cells concentrates on gametogenesis and attempts to model specific steps. Some of the technologies featured (such as IVM and the use of microfluidics) are already being applied clinically, while others are just emerging as potentially important.

Meanwhile, with the PCC schedule promising a feast of learning and attraction, news from the main programme is that a record number of abstracts had been received at ESHREs central office by submission deadline at end January. The total - of 2109 abstracts submitted - represents a new record and the first over 2000. The previous best was in Barcelona in the pre-covid days of 2018, when 1898 abstracts were received. After scoring and organisation into the selected oral communication sessions, the presentations will be made on the three days of the main programme, from Monday 26 June to Wednesday 28 June. The precongress courses will be held on Sunday 25 June, starting at 09.00

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Precongress courses at ESHRE23 characterised by practicality and ... - ESHRE

Embryology

Couple’s Child Has Deadly Cancer Gene Thanks to IVF Clinic’s … – The Daily Beast

Jason and Melissa Diaz thought they were giving their future child a shot at a healthy life when they opted for in vitro fertilization over natural conception. But according to a new lawsuit, what they got was nothing short of a disaster.

The California couple both carry genetic mutations: Melissa for BRCA-1, which predisposes carriers to breast cancer, and Jason for CDH1, which carries an elevated risk of stomach cancer.

Jason found out about his mutation in the summer of 2018, when he developed diffuse gastric cancer and was forced to undergo a gastrectomya full stomach removalwhen chemotherapy did not work. The life-altering procedure prevents patients from digesting food normally and causes chronic gastrointestinal pain, among other debilitating side effects.

When the Diazes decided to have children, they elected to go with IVF, so they could test the embryos for the genetic mutations before implanting them. According to the lawsuit, they wanted to achieve their dreams of parenthood without subjecting their children to the stomach cancer Jason and his family members had endured.

The fertility clinic they chose, HRC Fertility, advertises itself as having state-of-the-art embryology labs and remarkable lab personnel of highly trained and dedicated embryologists, according to the suit. It allegedly advertised their doctor, Bradford Kolb, as being known for helping to develop and implementing cutting edge technologies in the genetic screening of embryos.

From the beginning, they expressly advised HRC Fertility, its employees, and Dr. Kolb that they sought IVF with preimplantation genetic testing to avoid having a child with Jasons CDH1 mutation for hereditary diffuse gastric cancer, the suit states.

Jason and Melissa ultimately created five embryos with the clinic, only one of which did not carry either mutation, according to the suit. They transferred that embryo in August 2020, but Melissa ultimately miscarried.

Devastated but eager to try again, the suit claims, the Diazes asked their IVF coordinator to arrange for the implantation of a male embryo that the coordinator said carried the breast cancer mutation but not the stomach cancer mutation. (The couple considered this a safe choice because men are significantly less likely to develop breast cancer than women.)

Dr. Kolb transferred the embryo on Jan. 8, 2021, and Melissa gave birth to a boy in September. Jasons family threw a party for the couple to celebrate eliminating the CDH1 mutation from the Diaz family line, believing they had broken the curse that had doomed other family members to cancer and early death, the lawsuit states.

But the family was wrong. According to the suit, Dr. Kolb did not transfer a male embryo without the stomach cancer gene, because no such embryo existed. The IVF coordinator misrepresented the testing results and arranged for the transfer of a male embryo with the CDH1 mutation. The baby boy now has a more than 80 percent chance of developing stomach cancer, according to the suit.

We went through the difficult and expensive process of IVF so we could spare our children what Jason has had to endure, Melissa said at a press conference. We still cannot believe that after all we did ... our baby has the same genetic mutation we thought we escaped.

She added: Hes just such a happy baby, and to know the hurt in front of himthat he has to face for something we tried to preventit crushes me.

A spokesperson for HRC said in a statement that the Diazes had sought genetic testing and counseling outside of its facility, with a third party.

They wished to have a male embryo transferred, which we carried out according to the familys explicit wishes and in accordance with the highest level of care, the spokesperson said, adding that the company stand[s] by the professionalism and expertise of our medical staff and pride ourselves on adhering to the highest standards for patient care, patient records, results, and testing at all our locations.

According to the suit, the couples child will inevitably need to undergo a gastrectomy to prevent him from developing stomach cancer. They hope to delay the surgery until after he is finished developing, since removing the stomach before then could result in lifelong physical and cognitive impairments.

Jason, who saw two aunts die as a result of the cancer, called the results his greatest fear.

I wouldnt want anyone on earth to experience this type of pain, and now I will be forced to watch my own sonmy own flesh and bloodgo through this, he said. Every day my heart is hurting for my baby boy knowing the pain and challenges he has ahead of him.

Even if the child is able to delay the surgery until adulthood, he will still suffer from the pain, discomfort, and possible chronic diarrhea that afflicts many gastrectomy patients. The side effects may be so severe they will prevent him from taking certain jobs, according to the suit.

But the couple is not suing over the alleged wrongful implantation. Instead, they are alleging a coverup on the part of the fertility clinic, which they claim misled them even after the birth of their child.

According to the suit, the couple lived happily from September 2021 until July 2022, when they decided to try for another child. As part of this preparation, Melissa asked their new IVF coordinator to send over the report on the embryos they had created with HRC, so they could decide whichif anyof them they wanted to transfer.

What she saw on the report terrified her.

The embryo report, a copy of which is included in the complaint, contained handwritten notes that noted that the embryo transferred in January 2020the couples baby boywas positive for the stomach cancer mutation.

Melissa wrote back immediately, asking the coordinator to clarify whether the embryo theyd transferred carried the CDH1 gene. The coordinator did not respond. A week later, Melissa wrote again, saying the couple had been so stressed thinking of what our son will go through because of this genetic mutation.

Can you please double check that this is the correct report for our embryos? she wrote. Is there any way this could be a mistake? Again, the coordinator did not respond.

Eventually, the Diazes received a call from someone at HRC Fertility who admitted there had been a mistake, according to the suit, and called the couple in for a sit-down. When Melissa asked for a copy of her medical record, the clinic sent over a copy of the embryo report without the handwritten notes, the suit says, effectively removing the evidence of which embryo had been transferred.

HRC Fertility is one of the largest fertility clinics in the world, according to the suit, with nine offices across Southern California. The Pasadena office that the Diazes visited is a sprawling, 26,000-square-foot compound complete with luxurious VIP rooms, according to its website. According to the suit, the company is owned by Jinxin Fertility, one of the largest fertility companies in China.

Jinxin Fertility did not immediately respond to a request for comment.

HRC was also sued last summer by a same-sex couple who alleged that the center transferred a female embryo into their surrogate when they had explicitly requested a male. That suit, which also names Dr. Kolb as a defendant, is still pending in Los Angeles Superior Court.

A spokesperson for the company said last year that every child has value and limitless potential regardless of gender,'' and that they hoped the couple found love and value in their healthy child while so many across the country are struggling with reproductive issues.''

The Diazes have retained the services of Adam Wolf, an attorney known for his handling of IVF cases. Wolfs firm obtained a full copy of their medical record, handwritten notes included. They have initiated arbitration proceedings against HRC Fertility for the alleged wrongful transfer and are suing in California Superior Court for the alleged cover up.

The couple is requesting damages for their unimaginable mental anguish and for future lost wages and medical bills.

Tragically, this is yet another disaster in HRCs history of misusing patients genetic material and committing other grave fertility misconduct, Wolf said in a statement. In light of this history, I worry it will not be the last.

Excerpt from:
Couple's Child Has Deadly Cancer Gene Thanks to IVF Clinic's ... - The Daily Beast

Embryology

Three-parent baby technique could create babies at risk of severe disease – MIT Technology Review

Fortunately, both babies were born to parents without genes for mitochondrial disease; they were using the technique to treat infertility. But the scientists behind the work believe that around one in five babies born using the three-parent technique could eventually inherit high levels of their mothers mitochondrial genes. For babies born to people with disease-causing mutations, this could spell disasterleaving them with devastating and potentially fatal illness.

The findings are making some clinics reconsider the use of the technology for mitochondrial diseases, at least until they understand why reversion is happening. These mitochondrial diseases have devastating consequences, says Bjrn Heindryckx at Ghent University in Belgium, who has been exploring the treatment for years. We should not continue with this.

Its dangerous to offer this procedure [for mitochondrial diseases], says Pavlo Mazur, an embryologist based in Kyiv, Ukraine, who has seen one of these cases firsthand.

Mitochondria are little energy factories that float around in the cytoplasm of our cells. While most of our DNA is housed in the nucleus of a cell, a tiny fraction resides in mitochondria. This mitochondrial DNA, or mtDNA, is only passed down from mothers to their children.

This becomes a problem when the mtDNA carries a disease-causing mutation. Mitochondrial diseases are rare, affecting around 1 in 4,300 people in the US. And researchers are still working out how many of these cases are caused by mutations in mtDNA, as opposed to other genetic changes. But they can have serious effects, including blindness, anemia, heart problems, and deafness. Some are fatal.

To avoid this, scientists have developed techniques that allow them to use mtDNA from a donor, along with DNA from a mother and father. These are generally called mitochondrial replacement therapies, or MRT.

There are a few different ways of doing this, but most teams use one of two approaches. Some scoop out the nuclei of two eggs, one from a prospective parent and one from a donor. Then they put the would-be parents nucleus into the egg of the donor, which still contains the cytoplasm, the fluid outside the nucleus that holds the mitochondria. The resulting egg can then be fertilized with sperm, creating an embryo that technically has three genetic parents.

Others first create a fertilized egg, called a zygote. Then they collect the DNA-containing nucleus of this zygote, which can be transferred to another fertilized egg that has had its own nucleus removed. The resulting zygote also has three genetic parents.

No one knows exactly how many babies have been born through MRT. Several clinics have described a handful of cases, mainly at conferences. An official trial at Newcastle Fertility Centre, in the UK, was launched in 2017.

Since then, the Newcastle clinic has received regulatory approval to perform MRT for 30 couples with a risk of passing a mitochondrial disease to their children, according to published minutes of the statutory approvals committee of the UKs regulatory body, the Human Fertilisation & Embryology Authority (HFEA). But the team has been extremely tight-lipped about the study and has avoided sharing any results with other researchers in the field.

A few other teams have been trying to learn whether the treatment works for infertility. Many couples struggle with unexplained infertility, and it is thought that the mix of proteins in the cytoplasm of an egg might somehow contribute to their inability to conceive. Because MRT essentially involves swapping the cytoplasm of one egg with that of another, some believe it might help treat some of these cases, and boost the success rates of IVF.

Dagan Wells, a reproductive biologist at the University of Oxford, is a member of one such team. Wells and his colleagues have also been trying to work out how safe the procedure is. Research in cells in a dish and in monkeys suggests there is a chance that MRT might not always prevent mitochondrial diseases. If this happens in people, it could have serious consequences.

When you scoop out nuclear DNA, it is difficult to completely avoid taking some of the cytoplasmincluding mtDNAalong with it. Embryologists have managed to limit the resulting so-called carryover to less than 1% of the embryos total mtDNA. Usually that 1% shouldnt be a concern, because the other 99% is healthy, says Shoukhrat Mitalipov, an embryo biologist at Oregon Health & Science University, who is collaborating with Wells.

But research by Mitalipov and others has shown that this figure can increase over time. Scientists call the phenomenon reversion. This reversion could be a problem in couples where the mother carries a mitochondrial disease. If the percentage of bad mtDNA gets too high, it could cause disease in the child.

To find out if this could occur in people, Wells, Mitalipov and their colleagues used MRT in 25 cisgender heterosexual couples, each of which had been through between three and 11 failed cycles of IVF. All of the women had been diagnosed with some form of infertility, and none had ever managed to become pregnant.

MRT is banned in the US, and the Newcastle clinic is the only one with approval to perform MRT in the UK, so the treatments were done at a clinic in Greece.

In each case, a woman with infertility first underwent standard IVF procedures that allowed doctors to collect a glut of her eggs. The spindles of these eggs, which contain the nuclear DNA, were then removed and put into eggs from a fertile donor that had already had their own nuclei removed. The resulting eggs were then fertilized with the male partners sperm to create embryos.

Once the embryos had started to develop, scientists took a couple of cells from them to look at their mitochondrial DNA. In all of the embryos, the vast majority of mtDNA came from the donor, with less than 1% from the infertile woman.

The team used a total of 122 maternal eggs and 122 donor eggs to generate 85 with donor mtDNA that were successfully fertilized with sperm. Twenty-four of these developed into healthy-looking embryos, and 19 of them were transferred to a womans uterus, resulting in seven pregnancies. One woman miscarried at nine weeks, but the other six pregnancies resulted in healthy babies, all of whom were born between the end of 2019 and 2020.

The team has also been checking the levels of mitochondrial DNA in the babies since they were born. The scientists have looked at DNA samples taken from swabs of the babies cheeks, as well as their urine, cord blood, and other blood samples. For five of the babies, the levels of their mothers mtDNA has remained low, at less than 1%. But something strange has happened in one of the children.

At the embryo stage, less than 1% of this childs mtDNA came from the woman with bad mtDNA, while over 99% came from the donor. But by the time the baby was born, the balance had shiftedwith between 30% and 60% of the mtDNA coming from the mother. Its almost 50:50, says Wells. Thats a huge swing. The results were published in the journal Fertility and Sterility in February.

We were hoping we wouldnt see [reversion] in babies, says Mitalipov. Now we have data to show that this is realnot just in monkeys but in humans.

Its the first time weve seen it in a person, says Matthew Prior, the head of department at the Newcastle fertility center. He said his team has not seen reversion in any babies born following MRTbut he also wont confirm if any MRT babies have been born there.

But while this is the first published report, a second case has been reported by doctors who performed the procedure at the Nadiya clinic in Kyiv, Ukraine. At an online meeting in 2020, Pavlo Mazur, then an embryologist at the clinic, told his colleagues about a baby boy who had also shown reversion.

The baby was one of 10 born in a pilot trial of MRT for infertility, says Mazur. He and his colleagues used a slightly different techniquethe one that involves first creating an embryo and then removing its nucleus. This is also the approach used by the Newcastle team in the UK.

The baby, born in 2019, was the second child of a woman who had undergone MRT twice. Her first baby, a girl born in 2017, didnt show any reversion, says Mazurher levels of mtDNA from her mother remained below 1%. But despite the fact that the same team used eggs from the same woman, and performed the same procedure at the same clinic, her baby brother was born with around 72% of his mtDNA coming from his mother.

We found it earlier [than Wells and his colleagues], says Mazur. We just never published it.

Because the parents didnt carry disease-causing genes in their mitochondria, these babies should be fine, says Wells. But, he says, if this family were [carrying mtDNA mutations], this would be a big concern60% is high, and it may cause disease.

Wells thinks it is difficult to predict how many babies might be affected by reversion. If his team did another 100 rounds of MRT, they might not see another case. Or they could see 90, he says: The sample size is really too small to say anything about the frequency of this.

But Mitalipov is more confident. On the basis of the current study and his previous work in cells and monkeys, he believes there is around a 20% risk of reversion following MRT. In other words, if MRT is used to avoid passing on disease-causing mtDNA, theres a one in five chance the baby will inherit potentially dangerous levels of that mtDNA anyway. Its not very rare, he says.

The question is whether these odds are acceptable. For infertile couples without a history of mitochondrial diseases, the risks of using the technique appear to be low. But scientists using MRT in an effort to prevent mitochondrial diseases may be creating babies who could become severely unwell.

A 20% risk might be acceptable for some couples, says Prior. He says the results dont change anything for the trial at Newcastle, which will continue as planned. Obviously we will follow these results, and in due course well publish our own results, he says.

Heidi Mertes, a medical ethicist at Ghent University, says that it is important to think about what would-be parents would do if the technology were not available. If they would try for a baby regardless, then perhaps an 80% reduction in the risk of passing on disease-causing mtDNA is acceptable. But if they might otherwise consider using a donor egg, or adopting a child instead, then those are better alternatives, she says.

For Joanna Poulton, a mitochondrial geneticist at the University of Oxford, the 20% risk of reversion is very concerning. Whats more, the risk could end up being much greater than that. There are mutations where quite low levels can cause problems, she says. For some diseases, the level can be as low as 15%, she says.

And this is all complicated by the fact that mtDNA is messy. We can find different levels of mutations in different organs of a single person, and people with a mix of mtDNA can pass down either disease-causing or healthy genes in their eggs. A baby with low levels of bad mtDNA in the blood could still have high levels in the brain or muscles. This was also seen in the monkeys born using MRT, says Mitalipov. In a single animal, he says, the level of bad mtDNA could be 90% in the liver, and maybe 0% in the blood.

To complicate things even further, these levels can change over time. A lot of these mutations progressively increase in life so symptoms will happen much later, says Heindryckx. Some mitochondrial diseases dont make themselves apparent until people reach adolescence, for example. This all makes it very difficult to predict how many babies might be at risk of developing serious disease.

The finding also has implications for another, more established method of preventing mitochondrial diseases in babies.

Before MRT was developed, some clinics used a technique called preimplantation genetic testing (PGT) to screen embryos for disease. It is possible to pinch a couple of cells from an embryo created using IVF and check for disease-causing mutations. Prospective parents have the opportunity to avoid implanting any embryos that have high levels of bad mtDNA.

But the current findings suggest that PGT might not always work. If the levels of mtDNA can change as an embryo or fetus develops, theres still a chance that the baby could be born with a disease. This might happen if disease-causing mtDNA replicates better than the healthy mtDNA. The balance between levels of good and bad mtDNA can change for the worse.

We dont know, says Heindryckx. His is one of many centers that have performed PGT for couples with mitochondrial disease but didnt follow up on the resulting children, he says. Its a wake-up call for us to do it more.

We do know of one case in which it does not seem to have worked. A baby was born from an embryo that PGT revealed to have around 12% of the mothers bad mtDNA. But by the time the baby was born, the proportion had shot up to around 50%. This baby had a plethora of symptoms, including atypical brain development, behavioral problems, and signs that he had experienced a brain hemorrhage.

Only a small number of babies have been born after using PGT to screen for mitochondrial disease, so again, its difficult to draw conclusions. The French center that pioneered the treatment, and has been offering it since 2006, recently reported that it has only had 29 babies born this way, says Heindryckx. His own center has only used it for the births of four or five babies in the last 10 years. And, as with MRT reversion, theres a chance that babies who are disease free at birth might get sick as they get older.

Its alarming, says Heindryckx. We should also be following up the babies born after PGT, because it could be that this reversion is also happening there.

What does this mean for MRT in the meantime? While the Newcastle team plans to proceed with its trial, others caution that, for the time being at least, we should pause the use of MRT for mitochondrial disease, and instead study it in people who dont have these diseases, such as those with infertility.

Mazur himself refuses to use MRT for mitochondrial disease. And Heindryckx says the risk is too high for himwith a 20% risk of reversion, he says, there is no way the ethical committee at his institution would allow him to use MRT for mitochondrial disease.

Mertes says she has never been a fan of the MRT trials. Scientists knew beforehand that the trials were never going to be risk free, and that they involve a potential waste of perfectly good donor eggs and embryos. In the end, youre presenting an option to patients that is more dangerous than their alternative, she says.

Experimental treatments like MRT also help to reinforce the idea that its very important for parents to have a genetic connection to their children, says Mertes. Wouldnt it be wiser to question whether its so important to have that genetic connection if the price you have to pay is a health risk for your child? she asks. Parents can avoid all the risks that come with MRT by opting to use a donated egg in place of their own, or adopting a child, for example.

In the meantime, clinics that offer MRT need to update the information they provide so that people know that this is a very real risk that theyre taking, says Mertes. And both she and Prior think that the treatment should be restricted to those who need it or at least are adamant that they want a genetic link to their children.

Mitalipov is confident that scientists like himself will eventually come up with a solution to mitochondrial reversion. We just need to figure out why it happens, he says. So far, no clue but just give us time.

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Three-parent baby technique could create babies at risk of severe disease - MIT Technology Review

Embryology

UK ministers urged to consider changing law to allow genome editing of human embryos: Report – WION

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A citizens' jury in the United Kingdom (UK) has urged ministers to consider changing the law to allow scientists to carry out genome editing of human embryos for serious genetic conditions. The jury is made up of individuals whose lives have been affected by the hereditary disease. The report, published in Wellcome Connecting Science, has made "15 recommendations centered around transparency, inclusivity and equal access to treatment that should be considered in deciding whether to legalise editing of human embryos to treat genetic diseases."

According to Cambridge University on Tuesday (February 28), over 2.4 million people in the UK are currently living with a genetic condition. This includes disorders, such as cystic fibrosis or sickle cell anaemia, which are caused by variations in a single gene and can be inherited in families.

It is illegal (in the UK) to perform genome editing on embryos that lead to pregnancy, the university said. "The NHS does offer a service to couples who carry a heritable genetic trait to screen IVF embryos, meaning only embryos without the inherited condition are implanted. However, this approach is not suitable for everyone," it added.

The views of the individuals most affected by genetic conditions are timely due to two reasons, the 3rd International Summit on Human Genome Editing starting on Monday (March 6) and UK legislation due to be debated in parliament later this year.

Professor Anna Middleton,the leader of the project from Wellcome Connecting Science and the University of Cambridge,said that though all jurors have personal experience of an inherited genetic condition, their views on the editing of human embryos were varied, nuanced and complex.

"Many of the discussions were emotional, and the responsibility felt by the jurors to represent wider society in their deliberations was clear," Middleton said.

She added that when the Human Fertilisation and Embryology Act is debated in Parliament and discussions emerge on the editing of human embryos, it is imperative that the voices of patients are heard as part of this.

Andrea-Reid Kelly, one of the jurors said that before the jury, she did not know much about editing of human embryos or have a strong opinion about it. "Im a bit of a fence-sitter by nature. But by the end of the jury, I went from a neutral opinion to being in favour of parliamentary debate about potentially changing the law to allow editing of human embryos to treat genetic conditions," Kelly said.

Kelly was born with a significant heart condition, which was later learnt to be caused by Noonan syndrome. She said this is a genetic condition that can cause heart problems, distinctive facial features, small stature and specific learning difficulties such as dyslexia. She had heart surgery when she was four years old and then again when she was 33.

"So far as we know, neither of our daughters has Noonan syndrome. Because the gene that causes my case is unknown, we cant test them to know for sure," she added. Kelly also said that she met another person with the syndrome some years ago, and could identify with their experience and bond over challenges.

Another juror,Brenda Poku, suffers from sickle cell disease and her brother also has the condition. Sickle cell disease is a genetic condition caused by a faulty gene that affects the shape of red blood cells. One of the most common symptoms is bouts of pain, which are very unpredictable in timing and severity, sometimes requiring strong painkillers like morphine or even hospitalisation.

This condition is particularly common in people with African or Caribbean ancestry. Poku is originally from Ghana and moved to the UK to study for her doctorate. "I was originally a nurse, but now I research sickle cell disease from the perspective of patient experience and service provision," she said.

"Being in healthcare, I had some knowledge of genome editing before I took part in the citizens jury. There are advanced genome editing trials for sickle cell disease, with some of the participants having been cured. Researchers are monitoring them to make sure there are no unintended long-term side effects, but its likely there will be a cure for sickle cell in my lifetime," Poku said.

"During the jury event, I gained a new appreciation of why some people may want to take advantage of human embryo editing and would say that swayed me towards thinking it needed to be considered," she added.

(With inputs from agencies)

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UK ministers urged to consider changing law to allow genome editing of human embryos: Report - WION

Embryology

Surrogacy: the strict approach to consent – Lexology

When a child is born following a surrogacy arrangement, under English law, the surrogate will always be considered the childs legal mother, regardless of whether there is a genetic link between her and the baby.

If the surrogate is married or in a civil partnership at the time of conception, their spouse or civil partner will be the childs second legal parent (unless they did not consent to the fertility treatment). If the surrogate is not married or in a civil partnership, the intended father may be the childs legal father if they are genetically linked to the child.

To extinguish the surrogates legal parentage (and their spouses or civil partners) and be recognised as the childs legal parents under English law, the intended parents must apply to court for a parental order.

When deciding whether to make a parental order, the court will assess whether the criteria in s54/s54A Human Fertilisation and Embryology Act 2008 are met and whether it is in the childs best interests for a parental order to be made. One of the criteria requires the court to be satisfied that the surrogate (and her spouse or civil partner) have freely, and with full understanding of what is involved, agreed unconditionally to the making of the parental order. The surrogates consent cannot be given until after six weeks following the childs birth.

Over time, and owing to specific circumstances in some cases, the court has adopted a flexible approach towards some of the criteria, which has always been considered to be in the childs best interests. However, the requirement that the surrogate consent to the making of the parental order remains strict and there has been no flexibility when considering this.

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Surrogacy: the strict approach to consent - Lexology

Embryology

In politics, there’s no such thing as private faith – The Times

And so it begins. No longer able to bully, religion plays the victim card. Opinion writers from the religiously conservative right are whinnying the victimhood of their faith. The former Lib Dem leader Tim Farron pops up in at least two publications: Should our commitment to diversity, he whimpers in The Spectator, not extend to people with faith?

For more than a thousand years, faith has been bossing other people around, imprisoning them, burning them at the stake or cutting their heads off over such matters as sexuality, adultery, abortion, marriage, divorce, school curriculums, the essentially spherical nature of our planet, and more recently embryology and the right to die. But hey, whats this? Faith, forced at last into minority status, finds it no longer

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In politics, there's no such thing as private faith - The Times

Embryology

Delayed motherhood: Why more women are opting to freeze their … – Eve Magazine

The eggs can be safely preserved for more than 10 years (Photo: iStock)

I froze my eggs three years ago after I realised time is running out and I am still not in a stable relationship and not financially stable to have a baby, says 35-year-old, Liz, who chose anonymity.

Meeting her at her house in Nairobi, the bubbly, petite, 54 ft woman says that she did not know there existed a procedure, egg freezing and its benefits until she accidentally saw it in a movie.

The movie was an eye-opener. I discussed it with my mother, who was against it. That is why I have chosen not to reveal my name to you at this interview because I do not want anyone to know, she says laughing.

Sitting with me at her dining table, for this interview, Liz is subconsciously playing with a coaster as she explains how she faced her fears and decided to go for egg freezing.

I was really scared about the idea of removing my eggs. I was imagining the worst, but after research and consulting experts, I knew I will be okay, she says.

She explains that before freezing her eggs when she was 31, the planning started when she was 30 years since the procedure was quite costly.

It cost me almost half a million, hormonal injections, retrieval and the freezing of the eggs that costs Sh10,000 per month, so I paid for the whole year, that was Sh120,000 just for storage, she says.

For about two weeks, she took hormonal injections every day to stimulate the eggs.

I went to the hospital every single day for the injection, but there was an option of me doing it at home but I was too scared. After 10 days, they retrieved the eggs and froze them, she says.

She chose the procedure because she is yet to find the right partner.

I am single, the person I thought I would start a family with dumped me, she says, adding, I want to raise a complete family because I did not have that. My mother was a single mother. Right now, I am 35, maybe I will get married in 2-3 years which is almost 40. I dont want to risk conceiving, I would rather relax knowing my eggs are somewhere safe.

And Liz is not alone. More women, who plan to postpone having children in future are freezing their eggs.

Medical experts explain that egg freezing is a procedure where a womans eggs are harvested from her ovaries and then stored away from her body but can be accessed anytime she is ready to carry a pregnancy.

When a woman is ready, according to medics, she can access her frozen eggs to be conceived by being fertilized in a lab using a partners sperm or donor sperm. After the eggs are fertilized in a procedure that does not involve traditional sexual intercourse, the embryo is now implanted in her uterus or a surrogates uterus.

In Vitro Fertilisation expert, Dr Sarita Sukhija, founder of Myra IVF Centre, says that every woman is born with a certain set of eggs.

When a girl child is in the womb, she has around a million eggs and when she is born, she has about 30,0000-40,000 eggs in her ovaries. It is said that when a woman starts her period to the time she gets into menopause, she ovulates about 400 times, every month one egg ovulates and the rest do not grow, Dr Sukhija says.

She explains that the maximum fertility time is between 25-35 years since in this age group the eggs can be fertilised easily. After 35, the eggs become older and the embryos could be abnormal.

CANCER TREATMENT

The modern woman is engaging in the new science for many reasons.

Apart from the social one, where she, for instance, wants to focus on her career, some women in the country go for the procedure due to medical reasons.

Maryanne, not her real name, a 42-year-old mother of one, chose to freeze her eggs before starting her cancer treatment. I had my firstborn when I was 20. I want more children, so when I was diagnosed with breast cancer at the age of 31, I knew I had to freeze my eggs due to the effects of the treatment,

Maryanne hasnt used her eggs yet. Cancer went into remission, she got married last year and is now planning to start a family soon.

When a girl has her period, we call them on the second or third day of the cycle and start them on the hormonal injection. Because every month a certain set of eggs will come up on the ovaries like five eggs on one side, and six or seven eggs on the other side, so we want all those eggs stimulated, we give them the hormonal injections after checking their hormonal profiles and other blood tests, she says.

The hormonal injections are given continuously for 10 days and the patient is called periodically for an ultrasound scan to see how the eggs are growing.

Once the eggs are mature, the patient is called for egg retrieval. We go through the vagina ultrasound-guided. Because it is a slightly painful procedure, it is done under anaesthesia, it is short anaesthesia. So we extract the eggs and take them to the embryology lab. The embryologist will look at the eggs, there could be 3 kinds. Metaphase 2 (M2) are the mature ones ready for fertilisation. Metaphase 1 (M1) in between the immature ones known as Germinal vesicle (GV), Dr Sukhija.

There are different kinds of straws in which the eggs are loaded, with permanent markers. Every patient has a straw which is labelled. Once it goes into the liquid nitrogen, the name remains. In one tank there could be hundreds of samples every patient is marked with a name and ID, because there could be two patients with the same name. We have manual and computer records also, says Dr. Sukhija

If one woman has frozen around 10 eggs, they are frozen in groups of 3. The survival of the eggs is 80-90 per cent.

The hormone injections are given because more eggs are required. The injections are meant to stimulate the eggs which are in the ovary and can come out in one cycle.

Naturally, a woman will have only one egg. We want to freeze 10-15 eggs; some women might not have that in one cycle so we ask them to come back in the next cycle. We want more eggs to be frozen so that when we take them out we have enough that can be fertilised, she said.

Due to age and medical complications, not every woman can freeze her eggs. That is where donors come in. Donating is not harmful, the donors are paid between Sh 60,000-70,000. Its mostly college girls.

We encourage not more than two donations from one girl. After a gap of 6 months or 1 year, she can donate again, Dr Sukhija says.

Faith Kemunto, a Fertility Advocate, whose job is to do the matching, says that she carefully looks through the donor pool, reviewing donor characteristics, facial structure, skin tone and personality traits against the recipients characteristics profile.

Not an easy task to say the least. Recipients want to feel like the options I present to them will allow their future child to fit in with their family, and that they will look at this child and know they made the right decision. They come to me to help create their dreams. I have not had a complaint so far, she says.

Kemunto would send the client profile of the donors and if they feel some compatibility then they would start the counselling sessions and medical tests.

The new procedure has side effects that are caused by the fertility drugs that clients of the exercise use. The most common effects are abdominal pain, bloating of the stomach area, nausea, diarrhoea, and vomiting.

IVF specialists also say there are risks of miscarriage depending on the age at which one sought the service of freezing their eggs. Older women have a higher chance of having a miscarriage because they have older eggs.

Other team members in the process of egg freezing are the IVF Specialist, embryologist, anaesthetist, nurse, and a gynaecologist.

Embryologists play a critical role in an IVF clinic.

We are the scientific staff who help make babies happen, literally creating life in our hands. We are sometimes referred to as the caretakers like a mother of a patients sperm, eggs, or embryos because we are the nurturers of this new start of life, says a senior Embryologist at Myra IVF and Medical centre, Dr Satyawan.

Dr Satyawan says frozen embryos are stored and monitored at hospital facilities, usually a lab, or commercial reproductive medical centres.

The eggs can be safely preserved for more than 10 years.

There is a separate process for embryos from mothers that are HIV positive, says Dr Satyawan, adding, Yes, we have a separate storage facility at our center. We even separate such cases from ordinary cases. After that, we clean all our equipment (incubator and work area) properly, 2-3 times as per protocol.

Anne Kawira, a senior IVF nurse at Myra IVF and Medical Centre, says that her major role is educating patients and their partners about medication, administration, test preparation and specimen collection. I also teach patients how to administer IVF treatments assisting with Scans-Transvaginal scans/ultrasounds, Kawira says.

Moses Maina, an anaesthetist at the clinic, says that anaesthesia can be general where a drug is injected into patients bloodstream leading to loss of consciousness or regional anaesthetist where a drug can be injected through the patients lower back to cause numbness.

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Delayed motherhood: Why more women are opting to freeze their ... - Eve Magazine

Embryology

National Science Day & Rare Disease Day Observed At ILS … – Ommcom News

Bhubaneswar: The Institute of Life Sciences, Bhubaneswar celebrated the National Science Day 2023 with more than 300 students from 20 Colleges and Universities. The program had lectures by eminent scientists, live experiments, visit to ILS research infrastructure and discussions with scientists.

The live demonstrations showcased ILS research activities in the field of virology, protein structure and function, microscopy, embryology, malaria biology, biomaterials and human genetics.

A special session meet the scientists was organized to address science and career related questions from the participants. ILS Bio-Incubation center conducted a special program on entrepreneurship development and also showcased the products being developed at the bioincubation facility.

The day, 28th Februar,y is also observed as rare disease day globally to spread awareness about rare diseases. DBT-ILS is part of Department of Biotechnology funded Mission program on pediatric rare genetic diseases.

The scientists also took National Science Day as an opportunity to educate students about rare diseases that affect more than 300 million people worldwide. ILS scientist Dr Rajeeb Swain and Dr Mamoni Das coordinated the event

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National Science Day & Rare Disease Day Observed At ILS ... - Ommcom News

Embryology

Comparative Embryology – Developmental Biology – NCBI Bookshelf

The first known study of comparative developmental anatomy was undertaken by Aristotle in the fourth century b.c.e. He noted the different ways that animals are born: from eggs (oviparity, as in birds, frogs, and most invertebrates), by live birth (viviparity, as in eutherian mammals), or by producing an egg that hatches inside the body (ovoviviparity, as in certain reptiles and sharks). Aristotle also identified the two major cell division patterns by which embryos are formed: the holoblastic pattern of cleavage (in which the entire egg is divided into smaller cells, as it is in frogs and mammals) and the meroblastic pattern of cleavage (as in chicks, wherein only part of the egg is destined to become the embryo, while the other portionthe yolkserves as nutrition). And should anyone want to know who first figured out the functions of the placenta and the umbilical cord, it was Aristotle.

After Aristotle, there was remarkably little progress in embryology for the next two thousand years. It was only in 1651 that William Harvey concluded that all animalseven mammalsoriginate from eggs. Ex ovo omnia (All from the egg) was the motto on the frontispiece of his On the Generation of Living Creatures, and this precluded the spontaneous generation of animals from mud or excrement. This statement was not made lightly, for Harvey knew that it went against the views of Aristotle, whom Harvey still venerated. (Aristotle had thought that menstrual fluid formed the material of the embryo, while the semen acted to give it form and animation.) Harvey also was the first to see the blastoderm of the chick embryothat small region of the egg that contains the yolk-free cytoplasm that gives rise to the embryoand he was the first to notice that islands of blood cells form before the heart does. Harvey also suggested that the amnionic fluid might function as a shock absorber for the embryo.

As might be expected, embryology remained little but speculation until the invention of the microscope allowed detailed observations. In 1672, Marcello Malpighi published the first microscopic account of chick development. Here, for the first time, the neural groove (precursor of the neural tube), the muscle-forming somites, and the first circulation of the arteries and veinsto and from the yolkwere identified ().

Depictions of chick developmental anatomy. (A) Dorsal view (looking down at what will become the back) of a 2-day chick embryo, as depicted by Marcello Malpighi in 1672. (B) Ventral view (looking up at the prospective (more...)

With Malpighi begins one of the great debates in embryologythe controversy over whether the organs of the embryo are formed de novo (from scratch) at each generation, or whether the organs are already present, but in miniature form, within the egg (or sperm). The first view is called epigenesis, and it was supported by Aristotle and Harvey. The second view is called preformation, and it was reinvigorated with support from Malpighi. Malpighi showed that the unincubated* chick egg already had a great deal of structure. This observation provided him with reasons to question epigenesis. According to the preformationist view, all the organs of the adult were prefigured in miniature within the sperm or (more usually) the egg. Organisms were not seen to be developed, but rather unrolled.

The preformationist hypothesis had the backing of eighteenth-century science, religion, and philosophy (Gould 1977; Roe 1981, Pinto-Correia 1997). First, because all organs were prefigured, embryonic development merely required the growth of existing structures, not the formation of new ones. No extra mysterious force was needed for embryonic development. Second, just as the adult organism was prefigured in the germ cells, another generation already existed in a prefigured state within the germ cells of the first prefigured generation. This corollary, called embitment (encapsulation), ensured that the species would always remain constant. Although certain microscopists claimed to see fully formed human miniatures within the sperm or egg, the major proponents of this hypothesisAlbrecht von Haller and Charles Bonnetknew that organ systems develop at different rates and that embryonic structures need not be in the same place as those in the newborn.

The preformationists had no cell theory to provide a lower limit to the size of their preformed organisms (the cell theory arose in the mid-1800s), nor did they view humankind's tenure on Earth as potentially infinite. Rather, said Bonnet (1764), Nature works as small as it wishes, and the human species existed in that finite time between Creation and Resurrection. This view was in accord with the best science of its time, conforming to the French mathematician-philosopher Ren Descartes's principle of the infinite divisibility of a mechanical nature initiated, but not interfered with, by God. It also conformed to Enlightenment views of the Deity. The scientist-priest Nicolas Malebranche saw in preformationism the fusion of the rule-giving God of Christianity with Cartesian science (Churchill 1991; Pinto-Correia 1997).

The embryological case for epigenesis was revived at the same time by Kaspar Friedrich Wolff, a German embryologist working in St. Petersburg. By carefully observing the development of chick embryos, Wolff demonstrated that the embryonic parts develop from tissues that have no counterpart in the adult organism. The heart and blood vessels (which, according to preformationism, had to be present from the beginning to ensure embryonic growth) could be seen to develop anew in each embryo. Similarly, the intestinal tube was seen to arise by the folding of an originally flat tissue. This latter observation was explicitly detailed by Wolff, who proclaimed (1767), When the formation of the intestine in this manner has been duly weighed, almost no doubt can remain, I believe, of the truth of epigenesis. However, to explain how an organism is created anew each generation, Wolff had to postulate an unknown force, the vis essentialis (essential force), which, acting like gravity or magnetism, would organize embryonic development.

A reconciliation of sorts was attempted by the German philosopher Immanuel Kant (17241804) and his colleague, biologist Johann Friedrich Blumenbach (17521840). Attempting to construct a scientific theory of racial descent, Blumenbach postulated a mechanical, goal-directed force called the Bildungstrieb (development force). Such a force, he said, was not theoretical, but could be shown to exist by experimentation. A hydra, when cut, regenerates its amputated parts by rearranging existing elements (see Chapter 18). Some purposive organizing force could be observed in operation, and this force was a property of the organism itself. This Bildungstrieb was thought to be inherited through the germ cells. Thus, development could proceed through a predetermined force inherent in the matter of the embryo (Cassirer 1950; Lenoir 1980). Moreover, this force was believed to be susceptible to change, as demonstrated by the left-handed variant of snail coiling (where left-coiled snails can produce right-coiled progeny). In this hypothesis, wherein epigenetic development is directed by preformed instructions, we are not far from the view held by modern biologists that most of the instructions for forming the organism are already present in the egg.

The end of preformationism did not come until the 1820s, when a combination of new staining techniques, improved microscopes, and institutional reforms in German universities created a revolution in descriptive embryology. The new techniques enabled microscopists to document the epigenesis of anatomical structures, and the institutional reforms provided audiences for these reports and students to carry on the work of their teachers. Among the most talented of this new group of microscopically inclined investigators were three friends (born within a year of each other) who came from the Baltic region and who studied in northern Germany. The work of Christian Pander, Karl Ernst von Baer, and Heinrich Rathke transformed embryology into a specialized branch of science (and allowed the term embryology to be used to describe their work).

Pander studied the chick embryo for less than two years (before becoming a paleontologist), but in those 15 months, he discovered the three germ layers, the specific regions of the embryo that give rise to the specific organ systems (see ).

The ectoderm generates the outer layer of the embryo. It produces the surface layer (epidermis) of the skin and forms the nerves.

The endoderm becomes the innermost layer of the embryo and produces the digestive tube and its associated organs (including the lungs).

The mesoderm becomes sandwiched between the ectoderm and endoderm. It generates the blood, heart, kidney, gonads, bones, and connective tissues.

These three layers are found in the embryos of all triploblastic (three-layer) organisms. Some phyla, such as the porifera (sponges), cnidarians (sea anemones, hydra, jellyfish), and ctenophores (comb jellies) lack a true mesoderm and are considered diploblastic animals.

Pander (1817) also made observations that weighted the balance in favor of epigenesis. The germ layers, he noted, did not form their organs independently. Rather, each germ layer is not yet independent enough to indicate what it truly is; it still needs the help of its sister travelers, and therefore, although already designated for different ends, all three influence each other collectively until each has reached an appropriate level. Pander had discovered the tissue interactions that we now call induction. No tissue is able to construct organs by itself; it must interact with other tissues. (We will discuss the principles of induction more thoroughly in Chapter 6.) Thus, Pander felt that preformation could not be true, since the organs come into being through interactions between simpler structures.

Interestingly, the glory of Pander's book is its engravings; the artist, Eduard dAlton, drew details for which the vocabulary had not yet been invented. Today we can look at these drawings and see the four regions of the embryonic chick brain, even though these regions had not yet been separately defined or given names (; see Churchill 1991). The ability to make precise observations has been among the greatest skills of embryologists, and even today modern developmental biologists looking at gene expression patterns are rediscovering regions of the embryo that were observed by embryologists a century ago.

Rathke looked at the development of frogs, salamanders, fish, birds, and mammals, and emphasized the similarities in the development of all these vertebrate groups. During his 40 years of embryological research, he described for the first time the vertebrate pharyngeal arches (), which become the gill apparatus of fish but become the mammalian jaws and ears, (among other things, as we will see in ), the formation of the vertebrate skull, and the origin of the reproductive, excretory, and respiratory systems. He also studied the development of invertebrates, especially the crayfish. He is memorialized today in the name Rathke's pouch, the embryonic rudiment of the glandular portion of the pituitary. That he could see such a structure using the techniques available at that time is testimony to his remarkable powers of observation and his steady hand.

Pharyngeal arches (also called branchial arches and gill arches) in the embryo of the salamander Ambystoma mexicanum. The surface ectoderm has been removed to permit the easy visualization of these arches (highlighted) as they form. (Photograph courtesy (more...)

Jaw structure in the fish, reptile, and mammal. (A) Homologies of the jaws and gill arches as seen in the skull of the Paleozoic shark Cobeledus aculentes. (B) Lateral view of an alligator skull. The articular portion of the lower jaw articulates with (more...)

Karl Ernst von Baer extended Pander's studies of the chick embryo. He discovered the notochord, the rod of dorsalmost mesoderm that separates the embryo into right and left halves and which instructs the ectoderm above it to become the nervous system (). He also discovered the mammalian egg, that long-sought cell that everyone believed existed but no one had yet seen.

The notochord in the chick embryo. (A) Dorsal view of the 24-hour chick embryo. (B) A cross-section through the trunk shows the notochord and developing neural tube. By comparing Figures 1.2 and 1.4, you should see the remarkable changes between days (more...)

In 1828, von Baer reported, I have two small embryos preserved in alcohol, that I forgot to label. At present I am unable to determine the genus to which they belong. They may be lizards, small birds, or even mammals. allows us to appreciate his quandary. All vertebrate embryos (fish, reptiles, amphibians, birds, and mammals) begin with a basically similar structure. From his detailed study of chick development and his comparison of chick embryos with the embryos of other vertebrates, von Baer derived four generalizations (now often referred to as von Baer's laws), stated here with some vertebrate examples:

The similarities and differences between different vertebrate embryos as they proceed through development. They each begin with a basically similar structure, although they acquire this structure at different ages and sizes. As they develop, they become (more...)

The general features of a large group of animals appear earlier in development than do the specialized features of a smaller group. All developing vertebrates appear very similar shortly after gastrulation. It is only later in development that the special features of class, order, and finally species emerge. All vertebrate embryos have gill arches, notochords, spinal cords, and primitive kidneys.

Less general characters are developed from the more general, until finally the most specialized appear. All vertebrates initially have the same type of skin. Only later does the skin develop fish scales, reptilian scales, bird feathers, or the hair, claws, and nails of mammals. Similarly, the early development of the limb is essentially the same in all vertebrates. Only later do the differences between legs, wings, and arms become apparent.

The embryo of a given species, instead of passing through the adult stages of lower animals, departs more and more from them. The visceral clefts of embryonic birds and mammals do not resemble the gill slits of adult fish in detail. Rather, they resemble the visceral clefts of embryonic fish and other embryonic vertebrates. Whereas fish preserve and elaborate these clefts into true gill slits, mammals convert them into structures such as the eustachian tubes (between the ear and mouth).

Therefore, the early embryo of a higher animal is never like a lower animal, but only like its early embryo. Human embryos never pass through a stage equivalent to an adult fish or bird. Rather, human embryos initially share characteristics in common with fish and avian embryos. Later, the mammalian and other embryos diverge, none of them passing through the stages of the others.

Von Baer also recognized that there is a common pattern to all vertebrate development: the three germ layers give rise to different organs, and this derivation of the organs is constant whether the organism is a fish, a frog, or a chick.

1.1 The reception of von Baer's principles. The acceptance of von Baer's principles and their interpretation over the past hundred years has varied enormously. Recent evidence suggests that one important researcher in the 1800s even fabricated data when his own theory went against these postulates. http://www.devbio.com/chap01/link0101.shtml

By the late 1800s, the cell had been conclusively demonstrated to be the basis for anatomy and physiology. Embryologists, too, began to base their field on the cell. One of the most important programs of descriptive embryology became the tracing of cell lineages: following individual cells to see what they become. In many organisms, this fine a resolution is not possible, but one can label groups of cells to see what that area of the embryo will become. By bringing such studies together, one can construct a fate map. These diagrams map the larval or adult structure onto the region of the embryo from which it arose. Fate maps are the bases for experimental embryology, since they provide researchers with information on which portions of the embryo normally become which larval or adult structures. Fate maps of some embryos at the early gastrula stage are shown in . Fate maps have been generated in several ways.

Fate maps of different vertebrate classes at the early gastrula stage. All views are dorsal surface views (looking down on the embryo at what will be its back). Despite the different appearances of these adult animals, their fate maps (more...)

In certain invertebrates, the embryos are transparent, have relatively few cells, and the daughter cells remain close to one another. In such cases, it is actually possible to look through the microscope and trace the descendants of a particular cell into the organs they generate. This type of study was performed about a century ago by Edwin G. Conklin. In one of these studies, he took eggs of the tunicate Styela partita, a sea squirt that resides in the waters off the coast of Massachusetts, and he patiently followed the fates of each cell in the embryo until they differentiated into particular structures (; Conklin 1905). He was helped in this endeavor by the peculiarity of the Styela egg, wherein the different cells contain different pigments. For example, the muscle-forming cells always had a yellow color. Conklin's fate map was confirmed by cell removal experiments. Removal of the B4.1 cell (which should produce all the tail musculature), for example, resulted in the absence of tail muscles (Reverberi and Minganti 1946).

Fate map of the tunicate embryo. (A) The 1-cell embryo (left), shown shortly before the first cell division, with the fate of the cytoplasmic regions indicated. The 8-cell embryo on the right shows these regions after three cell divisions. (B) A linear (more...)

1.2 Conklin's art and science. The plates from Conklin's remarkable 1905 paper are online. Looking at them, one can see the precision of his observations and how he constructed his fate map of the tunicate embryo. http://www.devbio.com/chap01/link0102.shtml

The compound microscope. The compound microscope has been the critical tool of developmental anatomists. Mastery of microscopic techniques allows one to enter an entire world of form and pattern. [Click on Microscope]

Most embryos are not so accommodating as to have cells of different colors. Nor do all embryos have as few cells as tunicates. In the early years of the twentieth century, Vogt (1929) traced the fates of different areas of amphibian eggs by applying vital dyes to the region of interest. Vital dyes will stain cells but not kill them. He mixed the dye with agar and spread the agar on a microscope slide to dry. The ends of the dyed agar would be very thin. He cut chips from these ends and placed them onto a frog embryo. After the dye stained the cells, the agar chip was removed, and cell movements within the embryo could be followed ().

Vital dye staining of amphibian embryos. (A) Vogt's method for marking specific cells of the embryonic surface with vital dyes. (BD) Dorsal surface views of stain on successively later embryos. (E) Newt embryo dissected in a medial sagittal section (more...)

A variant of the dye marking technique is to make one area of the embryo radioactive. To do this, a donor embryo is usually grown in a solution containing radioactive thymidine. This base will be incorporated into the DNA of the dividing embryo. A second embryo (the host embryo) is grown under normal conditions. The region of interest is cut out from the host embryo and replaced by a radioactive graft from the donor embryo. After some time, the host embryo is sectioned for microscopy. The cells that are radioactive will be the descendants of the cells of the graft, and can be distinguished by autoradiography. Fixed microscope slides containing the sectioned tissues are dipped into photographic emulsion. The high-energy electrons from the radioactive thymidine will reduce the silver ions in the emulsion (just as light would). The result is a cluster of dark silver grains directly above the radioactive region. In this manner, the fates of different regions of the chick embryo have been determined (Rosenquist 1966).

One of the problems with vital dyes and radioactive labels is that they become diluted at each cell division. One way around this problem was the creation of fluorescent dyes that were extremely powerful and could be injected into individual cells. Fluorescein-conjugated dextran, for example, could be injected into a single cell of an early embryo. The descendants of that cell could then be seen by examining the embryo under ultraviolet light (). More recently, diI, a powerfully fluorescent molecule that becomes incorporated into lipid membranes, has also been used to follow the fates of cells and their progeny.

Fate mapping using a fluorescent dye. (A) Specific cells of a zebrafish embryo were injected with a fluorescent dye that will not diffuse from the cells. The dye was then activated by laser in a small region (about five cells) of the late cleavage stage (more...)

The problems with radioactive and vital dye marking include their dilution over many cell divisions and the laborious preparation of the slides. One permanent way of marking cells is to create mosaic embryos having different genetic constitutions. One of the best examples of this technique is the construction of chimeric embryos, consisting, for example, of a graft of quail cells inside a chick embryo. Chick and quail develop in a very similar manner (especially during early embryonic development), and a graft of quail cells will become integrated into a chick embryo and participate in the construction of the various organs. The substitution of quail cells for chick cells can be performed on an embryo while it is still inside the egg, and the chick that hatches will have quail cells in particular sites, depending upon where the graft was placed. The quail cells differ from the chick's in two important ways. First, the quail heterochromatin in the nucleus is concentrated around the nucleoli, making the quail nucleus easily distinguishable from chick nuclei. Second, there are cell-specific antigens that are quail-specific and can be used to find individual quail cells, even if they are in a large population of chick cells. In this way, fine-structure maps of the chick brain and skeletal system can be made (; Le Douarin 1969; Le Douarin and Teillet 1973).

Genetic markers as cell lineage tracers. (A) Grafting experiment wherein the cells from a particular region of a 1-day quail embryo have been placed into a similar region of a 1-day chick embryo. (B) After several days, the quail cells can be seen by (more...)

Histotechniques. Most cells must be stained in order to see them; different dyes stain different types of molecules. Instructions on staining cells to observe particular structures (such as the nucleus) are given here. [Click on Histotechniques]

One of the most important contributions of fate maps has been their demonstration of extensive cell migration during development. Mary Rawles (1940) showed that the pigment cells (melanocytes) of the chick originate in the neural crest, a transient band of cells that joins the neural tube to the epidermis. When she transplanted small regions of neural crest-containing tissue from a pigmented strain of chickens into a similar position in an embryo from an unpigmented strain of chickens, the migrating pigment cells entered the epidermis and later entered the feathers (). Ris (1941) used similar techniques to show that while almost all of the external pigment of the chick embryo came from the migrating neural crest cells, the pigment of the retina formed in the retina itself and was not dependent on the migrating neural crest cells. By using radioactive marking techniques, Weston (1963) demonstrated that the migrating neural crest cells gave rise to the melanocytes, and also to the peripheral neurons and the epinephrine-secreting adrenal medulla (, ). This pattern was confirmed in chick-quail hybrids, in which the quail neural crest cells produced their own pigment and pattern in the chick feathers. More recently, fluorescent dye labeling has followed the movements of individual neural crest cells as they form their pigment, adrenal, and neuronal lineages (see Chapter 13).

Neural crest cell migration. (A) Chick resulting from the transplantation of a trunk neural crest region from an embryo of a pigmented strain of chickens into the same region of an embryo of an unpigmented strain. The neural crest cells that gave rise (more...)

In addition to the travels of pigment cells, other wide-scale migrations include those of the primordial germ cells (which migrate from the yolky cells to the gonads and form the sperm and eggs) and the blood cell precursors (which undergo several migrations to colonize the liver and bone marrow).

As was pointed out by Matre-Jan in 1722, the egg examined by Malpighi may technically be called unincubated, but as it was left sitting in the Bolognese sun in August, it was not unheated.

Preformation was a conservative theory, emphasizing the lack of change between generations. Its principal failure was its inability to account for the variations known by the limited genetic evidence of the time. It was known, for instance, that matings between white and black parents produced children of intermediate skin color, an impossibility if inheritance and development were solely through either the sperm or the egg. In more controlled experiments, the German botanist Joseph Klreuter (1766) had produced hybrid tobacco plants having the characteristics of both species. Moreover, by mating the hybrid to either the male or female parent, Klreuter was able to revert the hybrid back to one or the other parental type after several generations. Thus, inheritance seemed to arise from a mixture of parental components.

From the same root as germination: the Latin germen, meaning sprout or bud. The names of the three germ layers are from the Greek: ectoderm from ektos (outside) plus derma (skin); mesoderm from mesos (middle), and endoderm from endon (within).

von Baer could hardly believe that he had at last found it when so many othersHarvey, de Graaf, von Haller, Prevost, Dumas, and even Purkinjehad failed. I recoiled as if struck by lightening I had to try to relax a while before I could work up enough courage to look again, as I was afraid I had been deluded by a phantom. Is it not strange that a sight which is expected, and indeed hoped for, should be frightening when it eventually materializes?

von Baer formulated these generalizations prior to Darwin's theory of evolution. Lower animals would be those appearing earlier in life's history.

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Comparative Embryology - Developmental Biology - NCBI Bookshelf

Embryology

A guided route – The Hindu

Uncertain about your career options? Low on self-confidence? This career counselling column may help

Uncertain about your career options? Low on self-confidence? This career counselling column may help

Dear Asha,

How creative are you? What do you enjoy? Art, drawing, colouring, out-of-the-box thinking? Art and Design courses (and careers eventually) include all sorts of exposure from UI to UX design, product design, video games design, multimedia art and animation, web design, exhibitions design, interior designing, fashion, jewellery and so on. First, identify if this is something that you would like to study more about and pursue as a subject. You will eventually know what your calling is and where your core interest lies.

Dear Sreedevi,

Indias Research and Analysis Wing gathers intelligence on other nations, especially those close to India, to protect it from any attacks, threats, and terrorist dangers by creating suitable policies, establishing international ties, and neutralising any threat to our democracy or safety. The UPSC exam is one route to join RAW (Group A officers from IAS, IPS, IFS and IRS). There are also other strategies for hiring. A candidate has to pass a psychological test and an interview. The eligibility criteria are graduation from a reputable institution and fluency in one foreign language. She/he must be an Indian with no criminal record. The age requirement is less than 56 years and the candidate must have more than 20 years of professional experience.

Dear Shasha,

Why did you enrol in this course? Work on the pros and cons of your choice and then arrive at your answer. Some good career options after this course are to work as a Research Associate, an Ethical hacker, a Penetration Tester, a Cyber Legal Service, a Security Code Auditor, and a Cryptographic Expert. It is also a well-rewarding industry for the right candidate.

Dear Vanshika,

You can apply for an M.Sc. in Clinical Embryology after your B.Sc. course. The eligibility criteria are B.Sc with at least one subject of Biological Science/ Biotechnology or MBBS from a recognised institution. Selection is done by an admission board strictly on merit. MET M.Sc. (Clinical Embryology) is conducted by Manipal Academy of Higher Education.

Disclaimer: This column is merely a guiding voice and provides advice and suggestions on education and careers.

The writer is a practising counsellor and a trainer. Send your questions to eduplus.thehindu@gmail.com with the subject line Off the edge.

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A guided route - The Hindu