An Embryo That Is Neither Male Nor Female

Article 1

An embryo that is neither male nor female

NewsRx Health, January 27, 2013

An embryo that is neither male nor female

By a News Reporter-Staff News Editor at VerticalNews Health -- So, is it a girl or a boy? This is the first question parents ask at the birth of an infant. Though the answer is obvious, the mechanism of sex determination is much less so. Researchers at the University of Geneva (UNIGE) attempt to shed light on this complex process by identifying the crucial role played by insulin and IGF1 and IGF2 growth factors, a family of hormones known for its role in metabolism and growth. In the absence of these factors at the time of sex determination, embryos do not differentiate into either male or female and have no adrenal glands. The results of this study, published in the journal PLOS Genetics, allow us to better understand sexual development and will eventually improve diagnosis and genetic counseling practices for individuals with disorders of sex development.

In mammals, sexual development is a long process beginning at conception when the sperm's transmission of an X or Y sex chromosome will determine the genetic sex of the embryo. The following developmental stages will translate this genetic sex into gonadal sex, that is, either ovaries or testes, which will secrete hormones that will masculinise or feminise the foetus.

The intention of the study conducted by Serge Nef, Professor at the Department of Genetic Medicine and Development at UNIGE, is to better understand the first stages of sexual development.

Growth, metabolism and reproduction

The researchers were interested in the role of a class of hormones, insulin-like growth factors (IGFs), and their receptors in cells. These factors, known to be involved in the regulation of metabolism and growth, also have a key role in the regulation of reproductive capacities of the individual, whether male or female. Reproductive function is, in fact, closely linked to metabolism and growth. This is actually quite logical: the growth of an individual cannot progress normally without adequate energy intake and there is no point in reproducing if this caloric intake is insufficient. This may explain why some women with anorexia have anovulatory cycles and may suffer from infertility. Conversely, people with morbid obesity also have significant disturbances in their fertility. Though it is now recognized that the interactions between metabolism, growth and reproductive capacity are regulated by common factors such as insulin and IGFs, Professor Nef's study shows that these interactions are even more important than previously believed because the insulin and IGF receptors are also essential for primary sex determination in mammals.

To analyze the impact of these hormones on sex determination, Professor Nef's group used genetically modified mice. The scientists genetically inactivated the receptors for insulin and IGFs in mouse embryos. They then discovered that in the absence of these factors, at the time of sex determination, the gonads of mutant embryos were unable to develop into testes or ovaries. As such, the embryo and its gonads remained stuck in a fully undifferentiated state for several days demonstrating the essential role of these hormones and growth factors in sexual differentiation.

In humans, cases of disorders of sex development are relatively common with about 1 newborn in every 3000 births being affected. Unfortunately, in the majority of cases, the genetic causes of such alterations remain unexplained. "This study provides a better understanding of the basic mechanisms of sexual development and is a step forward towards a better understanding of the causes of sexual ambiguities, which often remain unknown," states Professor Nef. "The research we are conducting will provide the opportunity to refine and improve clinical diagnosis of individuals with disorders of sex development."

"An embryo that is neither male nor female." NewsRx Health 27 Jan. 2013: 15. Student Resources In Context. Web. 26 Feb. 2013.

Article 2

Copyright: 2011 THE ASSOCIATED PRESS. All rights reserved. The information contained in the AP News report may not be published, broadcast or redistributed without the prior written authority of The Associated Press.

Could Prenatal DNA Testing Open Pandora's Box?

By Malcolm Ritter

This is the second story in a two-part series on fetal DNA testing and the ethical issues raised by it.

NEW YORK--Imagine being pregnant and taking a simple blood test that lays bare the DNA of your fetus. And suppose that DNA could reveal not only medical conditions like Down syndrome, but also things like eye color and height. And the risk for developing depression or Alzheimer's disease.And the chances of being gay.

So far that's still science fiction. But scientists have been taking some baby steps in that direction. And some ethics experts say it's time to start talking now about what that could mean for parents and society.

Scanning fetal DNA from a blood test will be "without question a major medical advance that promises to greatly improve current prenatal care," says Jaime King, an associate professor at the UC Hastings College of Law in San Francisco who studies genetic testing. But bringing it into practice "raises significant practical, legal, ethical and social challenges," she says.

"This really changes the experience of what it will be like to be pregnant and have a child," said Marcy Darnovsky of the Center for Genetics and Society in Berkeley, Calif. "I keep coming up with the word, game-changer."

She wonders if parents would withhold their commitment to a pregnancy until test results show a fetus is "good enough" to be born. And what, she asks, is good enough?

She and others worry about how well couples will be able to understand this flood of information, and just what should be revealed.

The issues have been discussed before. The DNA of a fetus has long been recoverable through medical procedures, with a small risk of miscarriage. But a blood test would be free of that risk, which should make many more women interested in it and doctors willing to test for a wider range of conditions, some experts say. And the results could come early enough to allow for an abortion before the pregnancy is even obvious.

The trigger for the new round of discussion is a couple of papers published last December. In preliminary results, two research teams showed that they could essentially reconstruct a baby's genetic makeup by recovering fragments of fetal DNA from the mother's bloodstream. That ability, plus the rapidly falling cost of analyzing DNA, would open the door to inspecting individual genes.

That would go well beyond the more accurate prenatal blood test for Down syndrome that some companies hope to market within a year.

Within five to 10 years, doctors may be able to test for 100 or 200 diseases, albeit many of them rare, estimates Stanford University law professor Hank Greely, who studies the implications of biomedical technologies.

Prenatal testing "is going to put a lot more information about the genetics of a child into the hands of a lot more parents," said King.

That knowledge has a flip side. "How much responsibility are we expecting people to take for the genetic makeup of any child they might have?" asks Josephine Johnston, a research scholar at the Hastings Center, a bioethics think tank near New York City.

If a child is born with a condition that could have been detected, the presence of the test changes that outcome "from something that happened to you, to something that you participated in," she says.

"That's a very big burden to place on would-be parents," she said, adding that it's hard for a pregnant woman to refuse any test for a medical condition because it feels like the responsible thing to do.

Johnston has personal experience; she gave birth to a girl just two years ago. When offered a medical screening test for the fetus, she generally felt compelled to take it.

"At the moment these things happen, it's just you there by yourself," she said. Some people might like that level of control, but others "would be happier to leave things up to chance a little more."

She said if she were pregnant again and offered a wider range of tests, she'd restrict herself to "really, really serious disabilities and disorders."

King, who had a son 18 months ago, said she wouldn't have wanted to know about any risk for incurable diseases that show up in adulthood. Those are "things that would have caused us to spend a lot of time worrying about what his future would look like even though there's nothing we could do about it," she said.

In the future, such testing could also look for other genes—some of which aren’t yet identified—that affect non-medical traits.

"If no limitations are put on, you can have a couple get a prenatal genetic test in the future saying their fetus has ... a 60 percent chance of having breast cancer at the age of 60 and a 30 percent chance of being gay," says Dr. Brian Skotko, a board member of the National Down Syndrome Society.

Since such information would come early enough for an abortion, Skotko says, "The ultimate question for society is, ‘What forms of human variation are valuable?’"

Then there's the possibility of direct-to-consumer companies stepping in to fill demand, King said. Couples who go that route may miss out on getting help in understanding the nuances of what the test results really mean, said Dr. Mary Norton, a Stanford professor of obstetrics and gynecology.

Once the prenatal information is available, another question arises, King said: Should a woman be allowed to get an abortion for any reason, even a trivial one like test results about height or eye color?

Some state governments have passed laws outlawing abortions on the basis of sex, she said. But it's not clear whether those are constitutional, and a woman might simply not reveal her true reasons for wanting the abortion, King said.

Skotko points out that people use their own personal perspective in deciding what they want for their children. Some couples who are deaf from a genetic condition already use current technology to avoid having children with normal hearing. "It's their lens by which they view the world, and they want a child who views the world through that same lens," he said.

Greely sees other concerns. Will the testing become so routine that women won't even realize they authorized it, and then be faced with information and an abortion decision they didn't necessarily want?

How can they be helped to make an informed decision on whether to be tested? And if offered a choice of genes to be tested, or results to be told about, who will help them sort through the long list to decide what they want to know? Few doctors are informed enough, and there aren't enough genetic counselors go around, he said.

The same problem arises later when it comes time to help couples understand what the results really mean, he said. "How do you tell somebody about 100 different genetic things?" he asked. "Who's going to do that? Who's going to listen to that? Who's going to pay for that?"

Results can be complex. For example, how is a woman supposed to balance a 25 percent increase in risk for one disease versus a 15 percent decrease in another, Darnovsky asks.

On a societal level, King said she's concerned that the prenatal diagnosis might become seen as a way of "curing" diseases by aborting fetuses that have them.

Greely recently spoke about prenatal diagnosis before the Presidential Commission for the Study of Bioethical issues, a federal advisory board. Valerie Bonham, executive director, said the commission may pursue the topic further as part of a project on DNA technology. "It's an important and emerging issue," she said.

Norton doesn't believe the arrival of a blood test for DNA analysis would raise all the issues some observers cite. But she thinks it's still a good idea to talk about what the new technology could mean.

"I think that it is always better and helpful and important to bring up all of these issues, whether they are likely to really become reality or not," she said.

"Once you've opened Pandora's box, it's harder to close it."

Ritter, Malcolm. "Could Prenatal DNA Testing Open Pandora's Box?." Newsday. 12 Jun 2011: n.p. SIRS Issues Researcher. Web. 14 Feb 2013.

Article 3

Ethics body backs potential "3-parent" IVF treatment

Reuters Health e-Line, June 13, 2012

Ethics body backs potential "3-parent" IVF treatment

By Kate Kelland

LONDON (Reuters) - "Three-parent" fertility treatments designed to prevent some incurable inherited diseases would be ethical and should go ahead as long as research shows they are likely to be safe and effective, a British medical ethics panel said on Tuesday.

The Nuffield Council on Bioethics said the potential treatments - known as three-parent in vitro fertilization (IVF) because the offspring have genes from a mother, father and from a female donor - should be offered to affected families together with full information and expert support.

"If these treatments are successful, these children would be among the first in the world to have a genetic connection to not two people, but three people," said Geoff Watts, who chaired a Nuffield inquiry into the issue. "There are a number of ethical questions that arise and needed to be considered."

Britain is widely considered to be at the forefront of research in this area, so ethical considerations and scientific advances here are likely to be closely watched around the world. Pro-life campaigners called the potential treatments dangerous.

Around one in 6,500 children worldwide are born with serious diseases caused by faulty mitochondrial DNA.

The new potential treatments involve intervening in the fertilization process to remove faulty mitochondrial DNA, which can lead to a range of inherited conditions including fatal heart problems, liver failure, brain disorders, blindness and muscular weakness.

Still at the research stage, the treatments effectively replace mitochondria, which act as tiny energy-generating batteries inside cells, so a baby does not inherit faults from its mother. Mitochondria are only passed down the maternal line.

"If further research shows these techniques to be sufficiently safe and effective, we think it would be ethical for families to use them ... provided they receive an appropriate level of information and support," said Watts.

Speaking at a briefing about the inquiry's conclusions, he said the new treatments could offer significant health and social benefits to affected families, allowing them to live "free from what can be very severe and debilitating disorders" and to have children without needing to adopt.

"This is a way in which parents can have children who are genetically related to them," Watts said. "And the descendants of any woman born via these therapies should inherit healthy mitochondria and be free of mitochondrial disorders."

PRO-LIFE CAMPAIGNERS OBJECT

There are various potential techniques. One being developed by scientists at Britain's Newcastle University, known as pronuclear transfer, swaps DNA between two fertilized human eggs. Another, known as the maternal spindle transfer, swaps material between the mother's egg and a donor egg before fertilization.

Medical experts welcomed the ethics report, saying it had rightly raised and clarified important issues in good time before potential treatments become available.

"Scientific progress that benefits human health is at its most effective when such questions can be raised and treatments are developed in a transparent and consultative manner," said Catherine Elliott of the Medical Research Council (MRC).

But pro-life campaigners at the Society for the Protection of Unborn Children (SPUC) criticized the research.

"Creating embryonic children in the laboratory abuses them, by subjecting them to unnatural processes. These techniques are both destructive and dangerous and therefore unethical," Anthony Ozimic, SPUC's communications manager, said in a statement.

Watts said the inquiry had also considered whether the proposed treatments would be a form of so-called "germline therapy" - since the changes resulting from replacing mitochondrial DNA would be passed on not only to the children, but also to future descendants of any girls born.

Although mitochondrial DNA swapping is not the same as altering the DNA inside a cell's nucleus, the Nuffield inquiry concluded it was nevertheless a form of germline therapy. But Watts stressed this did not mean the ethics body would approve any other forms of germline therapy, which are currently banned in Britain.

"Some people concerned about the idea of germline therapies may fear that if such treatments for mitochondrial gene disorders were approved, a slippery slope would be created towards comparable alterations to the nuclear genome," he said.