Genetic study explores why human pregnancy is unique

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Research data could aid efforts to prevent and treat adverse pregnancy outcomes, showing importance of progressive medicine

BUFFALO, NY – New study examines the evolutionary history of pregnancy, identifying hundreds of genes that have evolved to be turned on or off in humans’ wombs during early pregnancy, unlike a range of others animals.

The suite of genes identified include those believed to contribute to cell-to-cell communication, the regulation of the immune response and inflammation, and the ability of the human placenta to sink deep into the uterine wall. Such functions are important for the health of a pregnancy, in which the mother must harbor and coexist with a fetus containing foreign cells.

The findings help shed light on what makes human pregnancy uniquely human – an intriguing question, as human pregnancy is quite unusual compared to pregnancy in many other animals, says Vincent Lynch, PhD, associate professor of biological sciences at the University of Buffalo College of Arts and Sciences, and lead author of the article.

“Pregnancy in humans is different from pregnancy in other animals,” he says. “Human pregnancy lasts longer than it should. Labor and childbirth take longer than it should. The human placenta is really, really invasive. It sinks much deeper into the lining of the uterus than in other animals. And adverse pregnancy outcomes, such as premature birth and preeclampsia, appear to be much more common in humans than in other animals. “

The study was published on October 8 in eLife. The research was led by biologists Katie Mika, PhD, and Mirna Marinić, PhD, at the University of Chicago; Manvendra Singh, PhD, at Cornell University; and Lynch at UB. Co-authors included Joanne Muter, PhD, and Jan Joris Brosens, PhD, at Coventry & Warwickshire University Hospitals and the University of Warwick.

Data from the project could lay the groundwork for future studies to understand, prevent and treat various adverse pregnancy outcomes, demonstrating the power of the emerging field of evolutionary medicine.

Research has compared the activity of genes in the uterine lining of humans to that of other animals during pregnancy or while carrying eggs, including lizards, birds, monkeys and marsupials, and the platypus. . The study identified hundreds of genes that gained or lost uterine expression in the human lineage, focusing on the first trimester of pregnancy.

As the study reports, genes that have evolved to be turned on and off in the human uterus are “enriched in immune functions, signaling processes, and genes associated with adverse pregnancy outcomes such as infertility, recurrent spontaneous abortions, preeclampsia and premature birth. These genes include those that may contribute to a previously unknown maternal-fetal communication system (HTR2B), increase maternal-fetal immunotolerance (PDCD1LG2, also known as PD-L2), and promote vascular remodeling and deep invasion of the placenta (CORIN).

“Our article really highlights the useful role of evolutionary techniques in translational research,” says Mika, postdoctoral researcher in the Department of Human Genetics and the Department of Organismal Biology and Anatomy at the University of Chicago. “The three genes we have identified (HTR2B, PDCD1LG2 and CORIN) will advance work on signaling systems at the crucial mother-to-fetal interface, which impact the success and health of a pregnancy.”

“I was particularly intrigued by our discovery that the genes recruited were enriched in a serotonin signaling pathway,” says Marinić, postdoctoral researcher in the Department of Human Genetics and in the Department of Organism Biology and Anatomy. ‘University of Chicago. “Other researchers have already pointed out the potential role of serotonin and its derivatives at the onset of labor. I would be curious to study further what is the exact molecular mechanism by which serotonin influences the time of birth.

And although the article shows how evolutionary research can provide essential information for medicine, Lynch says simple curiosity is one of his main motivations as a scientist: “We just want to know how it works. ‘evolution. We are humans, so we want to know why humans are the way we are. Human pregnancy is really weird, so we want to understand what this weirdness is. “

Singh, a postdoctoral researcher in molecular biology and genetics at Cornell University, also commented on the importance of the findings, noting that, “During human pregnancies, the regulation of immunotolerance remains an enigma, especially when tissue invasion. embryonic is deeper than in the closest human relatives. It was remarkable to notice that over 900 genes are uniquely expressed during human pregnancy. This observation suggests that rewiring the regulatory sequences of these genes altered developmental processes and promoted the health of human pregnancy.

“By digging deeper, we also discovered that these genes have established functions to regulate immune responses and hormonal controls; for example, a serotonin receptor, mediators of interferon production, etc. As serotonin is produced and released by the brain, it is tempting to speculate that some of these genes may be involved in communication with the brain during pregnancy. Overall, although this study is of great clinical relevance, it also opens up multiple avenues for research on the mother-fetus interface. “

This study was supported by grants from the March of Dimes Chicago-Northwestern-Duke Prematurity Research Center and the Burroughs Welcome Fund Preterm Birth Initiative.


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