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At the frontier between two lives–the evolutionary origins of pregnancy

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Single-cell transcriptomic atlases of six mammalian species spanning the diversification of viviparity. Credit: Nature Ecology & Evolution (2025). DOI: 10.1038/s41559-025-02748-x

An international research team led by scientists from the University of Vienna has uncovered new insights into how specialized cell types and communication networks at the interface between mother and fetus evolved over millions of years. These discoveries shed light on one of nature's most remarkable innovations—the ability to sustain a successful pregnancy. The findings have just been published in Nature Ecology & Evolution.

Pregnancy that lasts long enough to support full fetal development is a hallmark evolutionary breakthrough of placental mammals—a group that includes humans. At the center of this is the fetal-maternal interface: the site in the womb where a baby's placenta meets the mother's uterus, and where two genetically distinct organisms—mother and fetus—are in intimate contact and constant interaction.

This interface has to strike a delicate balance: intimate enough to exchange nutrients and signals, but protected enough to prevent the maternal immune system from rejecting the genetically "foreign" fetus.

To uncover the origins and mechanisms behind this intricate structure, the team analyzed single-cell transcriptomes—snapshots of active genes in individual cells—from six mammalian species representing key branches of the mammalian evolutionary tree. These included mice and guinea pigs (rodents), macaques and humans (primates), and two more unusual mammals: the tenrec (an early placental mammal) and the opossum (a marsupial that split off from placental mammals before they evolved complex placentas).

A cellular 'atlas of mammal pregnancy'

By analyzing cells at the fetal-maternal interface, the researchers were able to trace the evolutionary origin and diversification of the key cell types involved. Their focus was on two main players: placenta cells, which originate from the fetus and invade maternal tissue, and uterine stromal cells, which are of maternal origin and respond to this invasion.

Using molecular biology tools, the team identified distinct genetic signatures—patterns of gene activity unique to specific cell types and their specialized functions. Notably, they discovered a genetic signature associated with the invasive behavior of fetal placenta cells that has been conserved in mammals for more than 100 million years.

This finding challenges the traditional view that invasive placenta cells are unique to humans, and reveals instead that they are a deeply conserved feature of mammalian evolution. During this time, the maternal cells weren't static, either. Placental mammals, but not marsupials, were found to have acquired new forms of hormone production, a pivotal step toward prolonged pregnancies and complex gestation, and a sign that the fetus and the mother could be driving each other's evolution.

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