Ancient secrets of a modern miracle: How pregnancy evolved

Pregnancy is one of nature’s most intricate achievements. At its core lies a delicate exchange between mother and fetus, where two genetically distinct bodies maintain close contact and constant communication.

This connection happens at the fetal-maternal interface – the meeting point between a baby’s placenta and the mother’s uterus – and it plays a critical role in allowing pregnancies to last long enough for full fetal development.

A new study by researchers from the University of Vienna explores how this unique interface came to be.

The research sheds new light on how cellular communication and cooperation evolved over millions of years to support successful pregnancies in placental mammals, including humans.

What mammals teach us about pregnancy

The team examined single-cell transcriptomes – snapshots of active genes in individual cells – across six mammalian species.

The species included humans, macaques, mice, guinea pigs, the tenrec (an early placental mammal), and the opossum (a marsupial whose evolutionary path diverged before complex placentas emerged).

The goal was to understand how the different cells at the fetal-maternal interface evolved and how their communication systems work.

The experts focused on two major players: placenta cells from the fetus that invade maternal tissue, and uterine stromal cells from the mother that respond to this invasion. These interactions need to be tightly controlled.

If the connection is too weak, the fetus may not get the nutrients it needs. But if it’s too strong, the mother’s immune system might recognize the fetus as foreign and attack it.

The genetic memory behind pregnancy

Using powerful molecular tools, the team uncovered genetic signatures tied to specific cell types and their unique functions.

One striking discovery was a shared genetic signature linked to the invasive behavior of fetal placenta cells – and this signature has remained in place for over 100 million years.

This challenges the long-held idea that these invasive cells are unique to humans. Instead, they appear to be a deeply rooted feature of mammalian biology.

Meanwhile, maternal cells weren’t standing still either. In placental mammals (but not in marsupials), new forms of hormone production emerged.

These hormonal innovations likely played a key role in extending pregnancy durations, giving developing babies more time in the womb. It also suggests that the evolution of pregnancy might have been shaped by a give-and-take between mother and fetus.

Cooperation or conflict?

To understand the tug-of-war – or possible teamwork – between mother and fetus, the researchers tested two evolutionary theories.

The first theory, called the “disambiguation hypothesis,” proposes that over time, certain hormonal signals became clearly assigned to either the mother or the fetus. This helps prevent confusion or manipulation between the two.

The results backed this theory up: hormones like WNT proteins, immune signals, and steroid hormones could be clearly traced to one source or the other.

Coordination between mother and fetus

The second theory, known as the “escalation hypothesis,” sees pregnancy as an arms race. Here, the fetus might ramp up growth signals while the mother tries to keep them in check.

Some evidence supported this theory, especially with genes like IGF2 that control growth. But overall, the data pointed more toward cooperation than conflict.

“These findings suggest that evolution may have favored more coordination between mother and fetus than previously assumed,” said Daniel J. Stadtmauer, lead author of the study.

“The so-called mother-fetus power struggle appears to be limited to specific genetic regions. Rather than asking whether pregnancy as a whole is conflict or cooperation, a more useful question may be: where is the conflict?”

Understanding the origins of pregnancy

The real breakthrough came from combining two techniques: single-cell transcriptomics and evolutionary modeling.

This allowed the team to compare gene activity in different species and even make predictions about what those interactions looked like in long-extinct ancestors.

“Our approach opens a new window into the evolution of complex biological systems – from individual cells to entire tissues,” said Silvia Basanta, co–first author of the study.

The research not only offers insights into how pregnancy evolved, but it could also help us better understand – and perhaps one day improve – how we treat complications during pregnancy.

By zooming in on the cellular scale, the team has given us a clearer picture of the deep evolutionary roots of one of life’s most remarkable biological collaborations.

The full study was published in the journal Nature Ecology & Evolution.

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