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Evolution, Fertility, Pregnancy, Research, Science, Stanford News, Stem Cells, Videos

Viral RNA essential for human development, say Stanford researchers

Viral RNA essential for human development, say Stanford researchers

Viruses are tricky, but we humans may be trickier still. Stanford stem cell biologists Vittorio Sebastiano, PhD, and Jens Durruthy-Durruthy, PhD, published a study today in Nature Genetics indicating that the genetic remnants of ancient viral infections that still linger in our genome are essential to early human embryonic development.

As Sebastiano explained in our release:

We’re starting to accumulate evidence that these viral sequences, which originally may have threatened the survival of our species, were co-opted by our genomes for their own benefit. In this manner, they may even have contributed species-specific characteristics and fundamental cell processes, even in humans.

The researchers, who talk about their work in the video above, relied on a new RNA sequencing technique to investigate the expression of what are called long-intergenic noncoding, or lincRNAs. These molecules don’t contain protein-making instructions, but instead affect the expression of other genes. They’ve been implicated in many important biological processes, including the acquisition of a developmental state called pluripotency that is necessary for a fertilized egg to develop into the cells and tissues of a growing fetus.

More from our release:

They identified more than 2,000 previously unknown RNA sequences, and found that 146 are specifically expressed in embryonic stem cells. They homed in on the 23 most highly expressed sequences, which they termed HPAT1-23, for further study. Thirteen of these, they found, were made up almost entirely of genetic material left behind after an eons-ago infection by a virus called HERV-H.

[…] After identifying HPAT1-23 in embryonic stem cells, Sebastiano and his colleagues studied their expression in human blastocysts — the hollow clump of cells that arises from the egg in the first days after fertilization. They found that HPAT2, HPAT3 and HPAT5 were expressed only in the inner cell mass of the blastocyst, which becomes the developing fetus. Blocking their expression in one cell of a two-celled embryo stopped the affected cell from contributing to the embryo’s inner cell mass. Further studies showed that the expression of the three genes is also required for efficient reprogramming of adult cells into induced pluripotent stem cells.

I can’t stop marveling at the close ties we have with viruses. It makes me think of the words of Michael Corleone in The Godfather: “Keep your friends close, and your enemies closer.” As Durruthy-Durruthy told me, “It’s fascinating to imagine how, during the course of evolution, primates began to recycle these viral leftovers into something that’s beneficial and necessary to our development.”

Previously: My baby, my… virus? Stanford researchers find viral proteins in human embryonic cellsMastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled  and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Video by Christopher Vaughan/Stanford Institute for Stem Cell Biology and Regenerative Medicine

Evolution, Infectious Disease, Microbiology, Pediatrics, Pregnancy, Research, Stanford News

Mastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled

Mastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled

and_virus_makes_four_fullI’m filing this finding firmly under the category of “Things I’m glad I didn’t know when I was pregnant.” (Other items include the abject terror of letting your teen get behind the steering wheel of a car for the first time, and the jaw-dropping number of zeros that can appear in a college financial aid package.) Recently, Stanford researchers found that the earliest stages of human development – those that occur within days of fertilization – may take place in a stew of viral proteins that lie in wait tucked inside the human genome. What do the viral proteins do? Who knows! Why are they popping up when we’re (arguably) at our most vulnerable? No idea!

Ugh. Like there’s not enough to worry about while growing another human inside your body.

I’m not being entirely fair here. Developmental biologist Joanna Wysocka, PhD, and graduate student Edward Grow, were some of the first researchers to show that ancient viral DNA sequences abandoned in our genome after long-ago infections can and do make viral proteins early in human development. I wrote about their finding on this blog earlier this year.

My article in the most recent issue of Stanford Medicine magazine expands on this story, describing how they made their finding and their future plans to learn more about our viral co-pilots. As I explain:

The finding raises questions as to who, or what, is really pulling the strings during human embryogenesis. Grow and Wysocka have found that these viral proteins are well-placed to manipulate some of the earliest steps in our development by affecting gene expression and even possibly protecting the embryo’s cells from further viral infection.

I’m often struck by how much parenting is like research. It’s a (seemingly) never-ending, but very rewarding, job. And for both, there’s clearly always lots to learn. As I write:

So, who’s in charge here? Us or the viruses? Or is there no longer any distinction? There’s certainly been plenty of evidence showing that humans are far from free operators when it comes to, well, pretty much anything. Our bodies are teeming masses of bacteria, viruses and even fungi that are collectively known as the microbiome. Many of these microorganisms, which are 10 times more numerous than our own cells, are essential to a healthy life, such as the gut bacteria that help us digest our food.

“What we’re learning now is that our ‘junk DNA,’ including some viral genes, is recycled for development in the first few days and weeks of life,” says [study co-author and former Stanford stem cell researcher Renee Reijo-Pera], who is now on the faculty of Montana State University. “The question is, what is it doing there?”

Previously: Stanford Medicine magazine tells why a healthy childhood mattersMy baby, my…virus? Stanford researchers find viral proteins in human embryonic cells and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Photo of Joanna Wysocka by Misha Gravenor

Obesity, Pregnancy, Research, Stanford News, Women's Health

Maternal obesity increases risk for stillbirth, new Stanford study finds

Maternal obesity increases risk for stillbirth, new Stanford study finds

bassinetWomen who are obese when they become pregnant are more likely than other expectant mothers to have a stillborn baby. But most studies of this relationship have included too few people to give detailed information about which obese women are at greatest risk, or which stages of pregnancy are most likely to be affected.

New Stanford research, led by Suzan Carmichael, PhD, and published online this week in PLOS ONE, changes that. The study used a very large California database of vital records on live births and stillbirths, allowing Carmichael’s team to compare 4,000 stillbirths – in which the baby was born dead after at least 20 weeks of pregnancy – to a control group of 1.1 million live births that followed full-term pregnancies.

With the large data set, the researchers were able to examine the effect of mothers’ race and ethnicity, whether the mothers had previously given birth, and how far along the pregnancies were at the time of the stillbirths. They excluded from analysis the cases in which an obvious fetal factor (such as a chromosomal abnormality) or a known maternal disease (such as diabetes) was probably responsible for the stillbirth.

What emerged is a complicated picture. Overall, greater obesity was linked with greater risk of stillbirth, with a 10-unit increase in body mass index equivalent to a 1.5- to twofold increase in stillbirth risk, a finding echoed by other recent research.

But the increase in risk wasn’t equal across all groups of women, or all stages of pregnancy. For instance, among Hispanic women who had never had a child before, the most extreme level of obesity conferred a five- to sixfold increase in the risk of having a stillbirth between 20 and 23 weeks of pregnancy and about a twofold increase in the risk of stillbirth near the baby’s due date, but was not linked with any change in the risk of having a stillbirth between 24 and 36 weeks’ gestation.

A few themes did emerge, however. Obesity consistently increased the risk for the very earliest stillbirths (between 20 and 23 weeks), regardless of a mother’s ethnicity or whether she had had other children. This is similar to another recent Stanford finding that obesity increases the risk for the earliest premature live births.

In the paper’s discussion section, the authors write:

Obesity and stillbirth are both complex, and many potential factors may contribute to their association. Stillbirth may stem from a variety of adverse conditions, including placental insufficiency, preterm onset of labor or rupture of membranes, infection and cord abnormalities. Obesity could contribute to any of these problems. In addition, obesity may contribute to lower sensitivity with regard to detection of fetal complications, on the part of monitoring tools or maternal ability to detect changes in fetal movement.

The authors hope their findings will help shed light on what causes stillbirth and how, perhaps, some cases might be prevented.

The research was funded by the March of Dimes Prematurity Research Center at Stanford University and the Stanford Child Health Research Institute.

Previously: Women who have had a stillbirth are more likely to experience long-term depression, study shows, Losing Jules: Breaking the silence around stillbirth and A call to “break the silence” of stillbirth
Photo by sincerely, brenda sue

Cardiovascular Medicine, Pediatrics, Pregnancy, Research

Higher blood sugar in pregnancy tied to heart defects in baby, even if mom isn’t diabetic

Higher blood sugar in pregnancy tied to heart defects in baby, even if mom isn't diabetic

five-heartsFor many years, doctors have known that women who had diabetes during pregnancy faced an increased risk of giving birth to a baby with a congenital heart defect. But now, for the first time, researchers have shown that the risk isn’t limited to women with diabetes. A new Stanford study, publishing today in JAMA Pediatrics, found that women who were carrying a fetus with tetralogy of Fallot, the most common cause of blue baby syndrome, had higher blood sugar levels on average than women carrying healthy fetuses, even if the mothers were not diabetic.

From our press release about the research:

“Diabetes is the tail end of a spectrum of metabolic abnormalities,” said James Priest, MD, the study’s lead author and a postdoctoral scholar in pediatric cardiology. “We already knew that women with diabetes are at significantly increased risk for having children with congenital heart disease. What we now know, thanks to this new research, is that women who have elevated glucose values during pregnancy that don’t meet our diagnostic criteria for diabetes also face an increased risk.”

The Children’s Heart Center at Lucile Packard Children’s Hospital Stanford (where Priest, who is also a pediatric cardiology fellow, sees patients) is already a world leader in treating children born with tetralogy of Fallot. Pediatric cardiothoracic surgeon Frank Hanley, MD, has developed a surgical technique called unifocalization that allows him to repair the defect in a single, long operation – which is safer than the alternative of putting babies and children through several open-heart surgeries. Many families come long distances so their children can receive the lifesaving surgery.

Although the Heart Center team is glad to be able to offer state-of-the-art treatment for kids who already have heart defects, they would be even happier to know how to prevent such defects from happening in the first place. Genetics plays into some heart defects, but in most cases, the cause is a mystery.

So this new study, though relatively small with 277 subjects, gives a clue that the Stanford team is eager to follow with other investigations:

“I’m excited by this research because it opens up a lot of questions about how physiologic processes in the mother may be related to congenital heart disease,” Priest said. “Most of the time we don’t have any idea what causes a baby’s heart defect. I aim to change that.”

The study’s senior author, Gary Shaw, DrPH, professor of pediatrics in neonatal and developmental medicine, added, “There are several other kinds of structural birth defects, in addition to heart defects, that have been linked with overt diabetes. This new work will motivate us to ask if underlying associations with moderately increased glucose levels may be similarly implicated in risks of some of these other birth defects.”

I also chatted with pediatric cardiologist and Heart Center director Stephen Roth, MD, who pointed out a practical advantage of the new finding that hadn’t occurred to me: We already know how to address elevated blood sugar with strategies such as dietary change, exercise and medications. If today’s discovery is replicated in larger studies, it wouldn’t be hard to translate it into action.

“It’s always wonderful to discover new information about the cause of a disease or class of diseases,” Roth told me. “And it’s particularly encouraging when we have the possibility of modifying the cause with existing therapies to reduce the likelihood that the disease occurs.”

Previously: Patient is “living to live instead of living to survive” thanks to heart repair surgery, Little hearts, big tools and When ten days = a lifetime: Rapid whole-genome sequencing helps critically ill newborn
Photo by emdot

Emergency Medicine, Pregnancy, Research, Surgery, Videos

Self-propelled powder moves against blood flow to staunch bleeding in hard-to-reach areas

Self-propelled powder moves against blood flow to staunch bleeding in hard-to-reach areas

If you nick your skin, it’s easy to stop the bleeding by applying a coagulant powder directly to the cut. Yet, bleeding wounds inside the body are beyond the reach of such blood-stopping powders.

Now, Christian Kastrup, PhD, an assistant professor at the University of British Columbia, and a team of researchers, biochemical engineers and emergency physicians, have developed a way to clot internal wounds by creating a self-propelled powder that moves against the flow of blood.

“Bleeding is the number one killer of young people, and maternal death from postpartum hemorrhage can be as high as one in 50 births in low resource settings so these are extreme problems,” Kastrup explained in a UBC press release. “People have developed hundreds of agents that can clot blood but the issue is that it’s hard to push these therapies against severe blood flow, especially far enough upstream to reach the leaking vessels. Here, for the first time, we’ve come up with an agent that can do that.”

To give blood-clotting powder a push, Kastrup and his colleagues added calcium carbonate to the coagulant powder. The carbonate forms porous micro-particles that latch onto the clotting agent (tranexamic acid). As the particles release carbon dioxide gas, fizzing and moving like mini-antacid tablets, they launch the clotting agent toward the source of bleeding.

More rigorous testing and development needs to be done before this agent is ready for use in humans, as the press release and study explain. But it’s possible that in the near future this powder could be used to treat otherwise unreachable cuts such as those in postpartum hemorrhages, sinus operations and internal combat wounds.

Previously: New obstetric hemorrhage tool kit released todayIn poorest countries, increase in midwives could save lives of mothers and their babiesTeen benefited by Stanford surgeon’s passion for trauma care
Video courtesy of UBC

Mental Health, Parenting, Pediatrics, Pregnancy, Public Health, Research, Women's Health

Sleep-deprivation and stress among factors contributing to smoking relapse after childbirth

Sleep-deprivation and stress among factors contributing to smoking relapse after childbirth

2473235415_0584b78298_zSmoking can make it more difficult to get pregnant and it can contribute to complications after conception and endanger the health of babies as they grow. For these reasons, many women quit smoking when they are trying to conceive and during pregnancy. But an estimated 40 percent of women in the United States who kick the nicotine habit for the health of their unborn child relapse within six months after delivery.

New research published in the journal Addiction suggests that the stress of becoming a parent could be a significant factor in why some moms resume smoking after childbirth. In the study, British researchers interviewed 1,000 mothers about factors that influenced their relapse or contributed to them staying smoke-free. Lead researcher Caitlin Notley, PhD, discussed the findings in a PsychCentral article:

One of the most striking things that we found is that women’s beliefs about smoking are a major barrier to remaining smoke-free. Many felt that smoking after the birth of their child was acceptable provided they protected their babies from secondhand smoke.

Their focus is, admirably, on the health of the baby, but they often do not think about the long-term health consequences for themselves as mothers.

We also found that women who saw smoking as a way of coping with stress were more likely to relapse. And that feeling low, lonely, tired, and coping with things like persistent crying were also triggers. Women reported that cravings for nicotine, which had lessened or stopped during pregnancy, returned.

The majority of women who had successfully remained smoke free said that the support of their partner was a strong factor. Partners who gave up smoking, or altered their own smoking behaviors, were a particularly good influence. And those who helped ease the stress of childcare were also praised by women who had resisted the urge to light up

In addition to receiving help from their partners, moms said support from health professionals was another positive contributor to them being able to resist urges to smoke and manage stress.

Previously: Study shows mothers receiving fertility treatments may have an elevated risk of depression, Examining how fathers’ postpartum depression affects toddlers, A telephone lifeline for moms with postpartum depression, What other cultures can teach us about managing postpartum sleep deprivation and Is postpartum depression more of an urban problem?
Photo by Samantha Webber

Genetics, In the News, Pregnancy, Research, Science, Women's Health

Maternal-fetal “chimera” cells: What do they actually do?

Maternal-fetal "chimera" cells: What do they actually do?

1292733380_3e6815a6d1_zAfter a woman is pregnant, fetal cells linger in her body long after her baby is brought out into the world. They cross the placenta and congregate in her thyroid, breasts, brain, scars… and elsewhere. The phenomenon is called “fetal microchimerism,” a reference to the hybrid monster of Greek mythology that strikes me as both whimsical and menacing.

But what do these cells do? An entertaining and informative National Geographic blog post highlights a recent review study published in BioEssays that seeks to answer this question. The evidence we have so far is contradictory and messy, not yielding much in the way of patterns: Sometimes cells collect more in diseased tissues, other times in healthy ones. But when viewed through an evolutionary lens, things start to make sense, argue the paper’s authors. These cells allow a baby to inadvertently influence her mother’s body in her own interest, which is sometimes – but not always – in the mother’s interest, too.

Writer Ed Yong explains:

Some of those changes, like faster healing, benefit the mother too. Others may not. For example, foetal cells could stimulate the breast to make more milk, either by releasing certain chemical signals or by transforming into glandular cells themselves. That’s good for the baby but perhaps not for the mother, given that milk takes a lot of energy to make—mothers literally dissolve their own bodies to create it. And if the foetal cells start dividing too rapidly in the breast, they might increase the risk of cancer.

Similarly, the thyroid gland produces hormones that control body temperature. If foetal cells integrate there and start dividing, they could ramp up a mother’s body heat, to a degree that benefits her baby but also drains valuable energy. And again, if they divide uncontrollably, they might increase the risk of cancer. Indeed, thyroid cancer is one of the only types that’s more common in women than men, but is not a reproductive organ like the ovaries or breasts.

Such influences would have developed gradually over hundreds of millions of years in a subtle evolutionary contest between mother and fetus – it is in the mother’s interest for the fetus to do well, but not to monopolize all her resources, so it’s not unlikely that mothers evolved counter-measures. The paper authors don’t have any conclusions yet, but their point is that within this evolutionary framework, it makes sense that fetal cells both help and harm the mother.

Previous research on microchimerism has only asked about such cells’ presence, not their function. The paper’s authors hope to organize a workshop to test some of the hypotheses they proposed, which means gathering microchimeric fetal cells and sequencing their genes, then working out which of the mother’s genes they are activating and whether these correlate with any traits like milk production or temperature. The possibilities for further research are immense:

And then, there’s the matter of cells that travel in the other direction—from the mother to the foetus. What do they do in their new homes? These paths can get even more complicated. It’s possible that the cells from one foetus can travel into its mother, hide out, and then into a sibling during a later pregnancy. “At one point, we started trying to draw family trees, and trying to work out where all the microchimerc cells could be going,” says [co-author Athena Aktipis, PhD]. “It got really messy.”

Previously: How a child’s cells may affect a mother’s long term health
Related: The yin-yang factor
Photo by Simone Tagliaferri

In the News, Parenting, Patient Care, Pregnancy, Public Health, Women's Health

Low-tech yet essential: Why parents are vital members of care teams for premature babies

Low-tech yet essential: Why parents are vital members of care teams for premature babies

3297657033_081d4f3630_zThanks to recent advances in medicine, technology and research, most premature babies born in the United States face better odds of surviving than ever before. Yet, the number of premature births in the U.S. remains relatively high, with a rate that’s on par with that of Somalia, Thailand and Turkey.

For the parents of a premature baby, an early birth can transform what was supposed to be a happy event into a stressful one, says Henry Lee, MD, an assistant professor of pediatrics at Lucile Packard Children’s Hospital Stanford. In a recent U.S. News & World Report article penned by Lee, he discusses why it’s important for parents, and beneficial for the baby, when parents are active members of the child’s medical team:

Giving birth to a preemie, especially when it’s unexpected, leaves many parents feeling unprepared and helpless. But we make it clear very early. “You, the parent, are a critical part of our medical team.” That’s right. Even in the heart of Silicon Valley where we’re located, two of our biggest assets are decidedly low-tech workers: the baby’s mom and dad.

Including parents in the care of preemies is a standard that was unheard of in the early days of neonatology, but is now used in leading NICUs for one critical reason: It works.

Here’s an example of how parents contribute. Studies have shown that skin-to-skin care, also known as kangaroo care, can have beneficial effects on preterm neonates, including improved temperature and heart rate stability. In many NICUs, you will see babies – clad only in a diaper and covered by a blanket – placed prone position on the chest of either the mother or the father. This intimate method of care provides a preterm baby a natural environment for rest, growth and healing.

No matter when a baby is born, term or preterm, families know their children best. A parent’s contribution is critical to treating these most vulnerable of newborns.

Previously: How Stanford researchers are working to understand the complexities of preterm birthNew research center aims to understand premature birth and A look at the world’s smallest preterm babies
Photo by Sarah Hopkins

In the News, Media, Medical Education, Medicine and Society, Myths, Pregnancy, Research

Reality TV influences perspectives on pregnancy, study shows

Reality TV influences perspectives on pregnancy, study shows

272417047_806faa2243_zA new University of Cincinnati study on the influence that television programs have on pregnant women has found that most women are more affected by TV representations of childbirth than they think.

The study, funded by the NSF and conducted by Danielle Bessett, PhD, assistant professor of sociology, followed a diverse group of 64 women over the course of two years and investigated how they understood their television viewing practices related to pregnancy and birth. It found that class, as measured by education level, had the greatest influence on whether a woman acknowledged television as a significant source of pregnancy-related information. Highly educated women and those who worked outside the home were more likely to dismiss TV, while those with less education and who were unemployed or took care of children at home were more likely to report watching and learning from such shows as TLC’s “Baby Story” and “Maternity Ward” and Discovery Health’s “Birth Day.”

The particularly interesting finding is that TV portrayals affect women’s perceptions even when they don’t believe they have an influence. Bessett developed the term “cultural mythologies of pregnancy” to describe how TV, film, media, and word of mouth create expectations about “the way things are.” Most reality TV and fictionalized programming presents childbirth as more dramatic and full of medical interventions than the majority of births really are, and these images made a lasting impression on women.

As quoted in the press release, Bessett says, “Hearing women –– even women who said TV had no influence on them –– trace their expectations back to specific television episodes is one of the few ways that we can see the power of these mythologies.” Many women mentioned pregnancy representations they had seen long before they got pregnant.

Women who reported watching TV considered it part of a comprehensive childbirth education program and would often evaluate the programs’ reliability, while women who disavowed television saw it as entertainment or education for children, likely from a desire to be seen as valuing science and medical expertise.

“If we believe that television works most insidiously or effectively on people when they don’t realize that it has power, then we can actually argue that the more highly educated women who were the most likely to say that television really didn’t have any effect on them, may in the end actually be more subject to the power of television than were women who saw television as an opportunity to learn about birth and recognized TV’s influence,” hypothesizes Bessett.

“This research implies that many women underestimate or under-report the extent to which their expectations of pregnancy and birth are shaped by popular media,” concludes Bessett, suggesting that “scholars must not only focus on patients’ professed methods for seeking information, but also explore the unrecognized role that television plays in their lives.”

Previously: New reality shows shine harsh light on teen pregnancy and Study: TV dramas can influence birth control use
Photo by johnny_zebra

Mental Health, Pregnancy, Research, Women's Health

Study shows mothers receiving fertility treatments may have an elevated risk of depression

Study shows mothers receiving fertility treatments may have an elevated risk of depression

5088785288_9f7a23f17a_zAn estimated one in four couples in developing countries encounter difficulties trying to conceive. In the United States, more than 7 million women have undergone fertility treatments and, as a result, millions of babies have been born through in-vitro fertilization.

While many may assume that failed fertility treatments would increase a woman’s risk of depression more than successful attempts that resulted in a live birth, research recently published in the journal ACTA Obstetricia et Gynecologica Scandinavica shows that the opposite may be true.

In the study, researchers from the University of Copenhagen analyzed data on 41,000 Danish women who had undergone fertility treatments. PsychCentral reports that “investigators discovered women who give birth after receiving fertility treatment are five times more likely to develop depression compared to women who don’t give birth.”

Lead author Camilla Sandal Sejbaek, PhD, discusses the results in the story:

The new results are surprising because we had assumed it was actually quite the opposite. However, our study clearly shows that women who become mothers following fertility treatment have an increased risk of developing depression in the first six weeks after birth compared to women who did not have a child.

Our study has not looked at why the depression occurs, but other studies indicate that it could be caused by hormonal changes or mental factors, but we cannot say for sure. We did not find any correlation between the number of fertility treatments and the subsequent risk of depression.

Previously: Stanford-developed fertility treatment deemed a “top medical breakthrough” of the year, Ask Stanford Med: Expert in reproductive medicine responds to questions on infertility, Image of the Week: Baby born after mom receives Stanford-developed fertility treatment and NIH study suggests progestin in infertility treatment for women with PCOS may be counterproductive
Photo by Big D2112

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