Category: Placenta

NIH Gears Up for a Closer Look at the Human Placenta

On By A.P.In Alan Guttmacher, Brian Cox, Carver College of Medicine, Human Placenta Project, Iowa, Iowa City, Kebmodee, Kimberly Leslie, March of Dimes, Medicine, National Institute of Child Health and Human Development, National Institutes of Health, NICHD, NIH, Placenta, University of Iowa, University of Iowa Hospitals and Clinics, University of TorontoLeave a comment

A placenta sustained you and every person ever born for 9 months, serving as your lungs and kidneys and pumping out hormones while you developed in the womb. Problems with this disk-shaped mass of tissue can contribute to everything from preterm births to diseases of middle age. Yet when a baby is born, hospitals usually throw the placenta away.

“It’s the least understood human organ,” says Alan Guttmacher, director of the National Institute of Child Health and Human Development (NICHD) in Bethesda, Maryland. “A large part of the scientific community never thinks about the placenta at all.” He and others hope to change that, however, by rallying researchers and funders, including other parts of the National Institutes of Health (NIH), around an effort to better understand the underappreciated organ. At an NICHD-sponsored workshop last week, some 70 researchers laid out their ideas for what NICHD calls the Human Placenta Project, including ways to better monitor the placenta during a pregnancy, and drugs to bolster it when it falters.

The human placenta forms primarily from cells that develop from the outer layer of fetal cells that surround an early embryo. Early in pregnancy, these trophoblasts invade the uterine wall and later develop a complex network of tiny projections called villi, which contain fetal blood vessels. This treelike structure of villi absorbs oxygen and nutrients from maternal blood; fetal waste and carbon dioxide meanwhile diffuse into the maternal bloodstream. Other specialized cells link the developing placenta to the umbilical cord. To avoid rejection by the mother’s immune system, the placenta employs various tricks, such as not expressing certain proteins. The placenta’s role during pregnancy is “an incredibly interesting biological time” that offers lessons for everything from cancer to organ transplantation, says physician-scientist Kimberly Leslie of the University of Iowa in Iowa City.

A malfunctioning, too small, or weakly attached placenta can starve the fetus, stunting its growth, and can also contribute to preeclampsia, or pregnancy-related high blood pressure, a condition that occurs in up to 6% of pregnancies and can require premature delivery of a baby. Adult diseases, too, ranging from cardiovascular disease to insulin resistance, seem to be linked to abnormal placenta morphology for poorly understood reasons.

During recent strategic planning at NICHD, researchers concluded that the placenta deserved closer study. “It came up repeatedly,” Guttmacher says. He expects that the Human Placenta Project will focus on understanding both the normal and abnormal placenta in real time during the course of pregnancy. It will also look for possible interventions—for example, a drug that would spur the growth of an abnormally small placenta.

Some at the workshop hope to adapt ultrasound and magnetic resonance imaging techniques now used to study the heart and brain to measure blood flow and oxygenation in the placenta. Injecting tracers, however, may be sensitive ethical territory. “People are very scared of doing things to pregnant women,” said placenta researcher Nicholas Illsley, of Hackensack University Medical Center in New Jersey, at the meeting. Another idea is to probe the mother’s bloodstream for cells and nucleic acids shed by the placenta as a window into the function of the organ.

Researchers also mused about creating a “placenta on a chip” that would mimic the tissue in the lab or developing molecular sensors that could monitor the placenta throughout pregnancy. “This sounds like science fiction, but if you showed me an iPhone 20 years ago, I would have said this was science fiction,” said Yoel Sadovsky, of the Magee-Womens Research Institute in Pittsburgh, Pennsylvania, at the meeting.

Attendees described a few immediate goals. One is to come up with standard definitions of a normal and abnormal placenta. Placenta morphology varies widely, and those from a healthy pregnancy can still have visible abnormalities, whereas those from sick babies often look completely normal, says systems biologist Brian Cox of the University of Toronto in Canada. Even before the NICHD meeting, the international community of placenta researchers had begun to coordinate their efforts by planning a website that will list existing placenta biobanks and help match collaborators.

At a time when NICHD’s budget is flat, money could be a limiting factor for the Human Placenta Project, which Guttmacher hopes will fund its first grants in 2016 and go for a decade or more. He expects that in addition to setting aside new money for the project, NICHD may give extra weight to high-quality grant applications focusing on the placenta. NICHD’s own contribution may be only “in the millions” of dollars, Guttmacher says. But he says eight other NIH institutes have expressed interest in contributing, as has the March of Dimes, an organization long focused on maternal and infant health. At long last, a throwaway organ may get the attention it deserves.

Thanks to Kebmodee for bringing this to the attention of the It’s Interesting community.

http://news.sciencemag.org/biology/2014/06/nih-gears-closer-look-human-placenta

New Study Ties Autism Risk to Creases in Placenta

On By A.P.In autism, Biological Psychiatry, Center for Autism Research at Children’s Hospital of Philadelphia, Cheryl K. Walker, Chris Mann Sullivan, Dr. Rajadhyaksha, Harvard Medical School, Harvey J. Kliman, Jonathan L. Hecht, Marbles, Medicine, MIND Institute, Neuropsychiatric Disease, Neuroscience, neuroscientist, New York Times, Placenta, Science, Tara Wenger, The Brain, trophoblast inclusions, UC Davis, University of California, Yale UniversityLeave a comment

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After most pregnancies, the placenta is thrown out, having done its job of nourishing and supporting the developing baby.

But a new study raises the possibility that analyzing the placenta after birth may provide clues to a child’s risk for developing autism. The study, which analyzed placentas from 217 births, found that in families at high genetic risk for having an autistic child, placentas were significantly more likely to have abnormal folds and creases.

“It’s quite stark,” said Dr. Cheryl K. Walker, an obstetrician-gynecologist at the Mind Institute at the University of California, Davis, and a co-author of the study, published in the journal Biological Psychiatry. “Placentas from babies at risk for autism, clearly there’s something quite different about them.”

Researchers will not know until at least next year how many of the children, who are between 2 and 5, whose placentas were studied will be found to have autism. Experts said, however, that if researchers find that children with autism had more placental folds, called trophoblast inclusions, visible after birth, the condition could become an early indicator or biomarker for babies at high risk for the disorder.

“It would be really exciting to have a real biomarker and especially one that you can get at birth,” said Dr. Tara Wenger, a researcher at the Center for Autism Research at Children’s Hospital of Philadelphia, who was not involved in the study.

The research potentially marks a new frontier, not only for autism, but also for the significance of the placenta, long considered an after-birth afterthought. Now, only 10 percent to 15 percent of placentas are analyzed, usually after pregnancy complications or a newborn’s death.

Dr. Harvey J. Kliman, a research scientist at the Yale School of Medicine and lead author of the study, said the placenta had typically been given such little respect in the medical community that wanting to study it was considered equivalent to someone in the Navy wanting to scrub ships’ toilets with a toothbrush. But he became fascinated with placentas and noticed that inclusions often occurred with births involving problematic outcomes, usually genetic disorders.

He also noticed that “the more trophoblast inclusions you have, the more severe the abnormality.” In 2006, Dr. Kliman and colleagues published research involving 13 children with autism, finding that their placentas were three times as likely to have inclusions. The new study began when Dr. Kliman, looking for more placentas, contacted the Mind Institute, which is conducting an extensive study, called Marbles, examining potential causes of autism.

“This person came out of the woodwork and said, ‘I want to study trophoblastic inclusions,’ ” Dr. Walker recalled. “Now I’m fairly intelligent and have been an obstetrician for years and I had never heard of them.”

Dr. Walker said she concluded that while “this sounds like a very smart person with a very intriguing hypothesis, I don’t know him and I don’t know how much I trust him.” So she sent him Milky Way bar-size sections of 217 placentas and let him think they all came from babies considered at high risk for autism because an older sibling had the disorder. Only after Dr. Kliman had counted each placenta’s inclusions did she tell him that only 117 placentas came from at-risk babies; the other 100 came from babies with low autism risk.

She reasoned that if Dr. Kliman found that “they all show a lot of inclusions, then maybe he’s a bit overzealous” in trying to link inclusions to autism. But the results, she said, were “astonishing.” More than two-thirds of the low-risk placentas had no inclusions, and none had more than two. But 77 high-risk placentas had inclusions, 48 of them had two or more, including 16 with between 5 and 15 inclusions.

Dr. Walker said that typically between 2 percent and 7 percent of at-risk babies develop autism, and 20 percent to 25 percent have either autism or another developmental delay. She said she is seeing some autism and non-autism diagnoses among the 117 at-risk children in the study, but does not yet know how those cases match with placental inclusions.

Dr. Jonathan L. Hecht, associate professor of pathology at Harvard Medical School, said the study was intriguing and “probably true if it finds an association between these trophoblast inclusions and autism.” But he said that inclusions were the placenta’s way of responding to many kinds of stress, so they might turn out not to be specific enough to predict autism.

Dr. Kliman calls inclusions a “check-engine light, a marker of: something’s wrong, but I don’t know what it is.”

That’s how Chris Mann Sullivan sees it, too. Dr. Sullivan, a behavioral analyst in Morrisville, N.C., was not in the study, but sent her placenta to Dr. Kliman after her daughter Dania, now 3, was born. He found five inclusions. Dr. Sullivan began intensive one-on-one therapy with Dania, who has not been given a diagnosis of autism, but has some relatively mild difficulties.

“What would have happened if I did absolutely nothing, I’m not sure,” Dr. Sullivan said. “I think it’s a great way for parents to say, ‘O.K., we have some risk factors; we’re not going to ignore it.’ ”

Thanks to Dr. Rajadhyaksha for bringing this to the attention of the It’s Interesting community.

Homosexuality may start in the womb

On By A.P.In Australian black swans, California gulls, Darwin, epigenetics, gay genes, homosexuality, Human Behavior, Marlene Zuk, Placenta, Relationship, Santa Barbara, Science, sexuality, sheep, testosterone, The Brain, The Quarterly Review of Biology, Twin Cities, William Rice, Y chromosomeLeave a comment

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From a strictly Darwinian viewpoint, homosexuality shouldn’t still be around. It isn’t the best way to pass along one’s genes, and to complicate the picture further, no “gay genes” have even been identified. According to a newly released hypothesis, the explanation may not lie in DNA itself. Instead, as an embryo develops, sex-related genes are turned on and off in response to fluctuating levels of hormones in the womb, produced by both mother and child. This tug of war benefits the unborn child, keeping male or female development on a steady course even amid spikes in hormones. But if these so-called epigenetic changes persist once the child is born and has children of its own, some of those offspring may be homosexual, the study proposes.

Evolutionary geneticist William Rice of the University of California, Santa Barbara, felt there had to be a reason why homosexuality didn’t just fade away down the generations. Research estimates that about 8% of the population is gay, and homosexuality is known to run in families. If one of a set of identical twins is gay, there’s a 20% probability that the other will be, too.

Furthermore, Rice notes, “homosexuality isn’t just a human thing.” Among California gulls, which he watches from his office window, about 14% of pairs are female-female. In Australian black swans, some 6% of pairs are male-male, and 8% of male sheep are attracted exclusively to male partners.

But many genetic screens have failed to turn up genes that are responsible for sexual orientation. So to find out what makes homosexuality persist, Rice and colleagues began a comprehensive survey of the literature.

According to conventional wisdom, an embryo becomes a boy when a gene on the Y chromosome triggers the development of testes, which then begin to produce male sex hormones, including testosterone, at about the 8th week of gestation. With no Y chromosome and hence no testosterone, the embryo becomes a girl.

But testosterone doesn’t explain everything, the researchers found. For one thing, female fetuses are exposed to small amounts of the hormone from their adrenal glands, the placenta, and the mother’s endocrine system. At many key points of gestation, male and female fetuses are often exposed to similar amounts of testosterone. Levels of the hormone can even be higher than normal in females and lower than normal in males without any effect on genital or brain structure.

Rice and his co-workers were more intrigued by studies showing that male and female fetuses respond differently to the hormones that surround them, even when one hormone is temporarily higher. In their study, published online today in The Quarterly Review of Biology, the authors propose that differences in sensitivity to sex hormones result from “epigenetic” changes. These are changes that affect not the structure of a gene but when, if, and how much of it is activated—by chemically altering a gene’s promoter region or “on” switch, for example. Epigenetic changes at key points in the pathway through which testosterone exerts its effects on the fetus could blunt or enhance the hormone’s activity as needed, the authors suggest.

Although epigenetic changes are usually temporary, they involve alterations in the proteins that bind together the long strands of DNA. Thus, they can sometimes be handed down to offspring. According to the hypothesis, homosexuality may be a carry-over from one’s parents’ own prenatal resistance to the hormones of the opposite sex. The “epi-marks” that adjusted parental genes to resist excess testosterone, for example, may alter gene activation in areas of the child’s brain involved in sexual attraction and preference. “These epigenetic changes protect mom and dad during their own early development,” Rice says. The initial benefit to the parents may explain why the trait of homosexuality persists throughout evolution, he says.

“The authors have done a terrific job providing a mechanism for genetic variation, especially a variation that might not be expected to persist because it’s so tightly bound to reproduction,” says evolutionary biologist Marlene Zuk of the University of Minnesota, Twin Cities. But she adds that to go from changes in gene expression to why someone is attracted to a person of the same sex is a question for which science may never fill in all the blanks.

http://news.sciencemag.org/sciencenow/2012/12/homosexuality-may-start-in-the-w.html?ref=hp

Mother-Child Connection: Scientists Discover Children’s Cells Living in Mothers’ Brains, Including Male Cells Living in the Female Brain for Decades

On By A.P.In Alzheimer's disease, bond, breast cancer, Chimera, chimerism, Communication, DNA, fetus, human, immune system, Microchimerism, mother-child connection, multiple pregnancies, Multiple Sclerosis, Nature, Neuropsychiatric Disease, Neuroscience, neuroscientist, nursing, Placenta, Pregnancy, Relationship, Science, Scientific American, stem cells, The Brain, twinsLeave a comment

scientists-discover-childrens-cells-living-in-mothers-brain_1

 

The link between a mother and child is profound, and new research suggests a physical connection even deeper than anyone thought. The profound psychological and physical bonds shared by the mother and her child begin during gestation when the mother is everything for the developing fetus, supplying warmth and sustenance, while her heartbeat provides a soothing constant rhythm.

The physical connection between mother and fetus is provided by the placenta, an organ, built of cells from both the mother and fetus, which serves as a conduit for the exchange of nutrients, gasses, and wastes. Cells may migrate through the placenta between the mother and the fetus, taking up residence in many organs of the body including the lung, thyroid muscle, liver, heart, kidney and skin. These may have a broad range of impacts, from tissue repair and cancer prevention to sparking immune disorders.

It is remarkable that it is so common for cells from one individual to integrate into the tissues of another distinct person. We are accustomed to thinking of ourselves as singular autonomous individuals, and these foreign cells seem to belie that notion, and suggest that most people carry remnants of other individuals. As remarkable as this may be, stunning results from a new study show that cells from other individuals are also found in the brain. In this study, male cells were found in the brains of women and had been living there, in some cases, for several decades. What impact they may have had is now only a guess, but this study revealed that these cells were less common in the brains of women who had Alzheimer’s disease, suggesting they may be related to the health of the brain.

We all consider our bodies to be our own unique being, so the notion that we may harbor cells from other people in our bodies seems strange. Even stranger is the thought that, although we certainly consider our actions and decisions as originating in the activity of our own individual brains, cells from other individuals are living and functioning in that complex structure. However, the mixing of cells from genetically distinct individuals is not at all uncommon. This condition is called chimerism after the fire-breathing Chimera from Greek mythology, a creature that was part serpent part lion and part goat. Naturally occurring chimeras are far less ominous though, and include such creatures as the slime mold and corals.

 Microchimerism is the persistent presence of a few genetically distinct cells in an organism. This was first noticed in humans many years ago when cells containing the male “Y” chromosome were found circulating in the blood of women after pregnancy. Since these cells are genetically male, they could not have been the women’s own, but most likely came from their babies during gestation.

In this new study, scientists observed that microchimeric cells are not only found circulating in the blood, they are also embedded in the brain. They examined the brains of deceased women for the presence of cells containing the male “Y” chromosome. They found such cells in more than 60 percent of the brains and in multiple brain regions. Since Alzheimer’s disease is more common in women who have had multiple pregnancies, they suspected that the number of fetal cells would be greater in women with AD compared to those who had no evidence for neurological disease. The results were precisely the opposite: there were fewer fetal-derived cells in women with Alzheimer’s. The reasons are unclear.

Microchimerism most commonly results from the exchange of cells across the placenta during pregnancy, however there is also evidence that cells may be transferred from mother to infant through nursing. In addition to exchange between mother and fetus, there may be exchange of cells between twins in utero, and there is also the possibility that cells from an older sibling residing in the mother may find their way back across the placenta to a younger sibling during the latter’s gestation. Women may have microchimeric cells both from their mother as well as from their own pregnancies, and there is even evidence for competition between cells from grandmother and infant within the mother.

What it is that fetal microchimeric cells do in the mother’s body is unclear, although there are some intriguing possibilities. For example, fetal microchimeric cells are similar to stem cells in that they are able to become a variety of different tissues and may aid in tissue repair. One research group investigating this possibility followed the activity of fetal microchimeric cells in a mother rat after the maternal heart was injured: they discovered that the fetal cells migrated to the maternal heart and differentiated into heart cells helping to repair the damage. In animal studies, microchimeric cells were found in maternal brains where they became nerve cells, suggesting they might be functionally integrated in the brain. It is possible that the same may true of such cells in the human brain.

These microchimeric cells may also influence the immune system. A fetal microchimeric cell from a pregnancy is recognized by the mother’s immune system partly as belonging to the mother, since the fetus is genetically half identical to the mother, but partly foreign, due to the father’s genetic contribution. This may “prime” the immune system to be alert for cells that are similar to the self, but with some genetic differences. Cancer cells which arise due to genetic mutations are just such cells, and there are studies which suggest that microchimeric cells may stimulate the immune system to stem the growth of tumors. Many more microchimeric cells are found in the blood of healthy women compared to those with breast cancer, for example, suggesting that microchimeric cells can somehow prevent tumor formation. In other circumstances, the immune system turns against the self, causing significant damage. Microchimerism is more common in patients suffering from Multiple Sclerosis than in their healthy siblings, suggesting chimeric cells may have a detrimental role in this disease, perhaps by setting off an autoimmune attack.

This is a burgeoning new field of inquiry with tremendous potential for novel findings as well as for practical applications. But it is also a reminder of our interconnectedness.

http://www.scientificamerican.com/article.cfm?id=scientists-discover-childrens-cells-living-in-mothers-brain