New Study Unlocks Secrets of High-Elevation Pregnancies

Fetus Third Trimester Pregnancy Human Development Illustration

Researchers at the University of Montana uncovered genetic traits that help highland mice maintain healthy pregnancies at high altitudes, hinting at evolutionary strategies against hypoxia-related complications and opening avenues for human medical advancements.

Pregnancy at elevated altitudes often leads to low birth weights and various complications. These issues are seen across a broad spectrum of mammals, from deer mice to humans.

A study from the University of Montana has uncovered genetic factors that enable specific highland mouse communities to protect their developing fetuses in these higher terrains. The research was recently published in the Proceedings of the National Academy of Sciences.

“Understanding how deer mice survive and thrive at high elevations not only informs our understanding of basic evolutionary processes, it may also one day provide clues for treating a range of related disorders in humans,” said Zac Cheviron, a UM researcher and biology associate professor.

The work was led by Kate Wilsterman, a UM postdoctoral researcher who has since joined the faculty of Colorado State University. Cheviron, UM biology Professor Jeff Good, and former UM postdoctoral researcher Rena Schweizer were her chief collaborators in Montana.

Rena Schweizer, Zac Cheviron and Jeff Good

Researchers (left to right) Rena Schweizer, Zac Cheviron, and Jeff Good, shown here in a University of Montana lab, studied how deer mice protect developing fetuses at higher elevations. Credit: UM photo by Ridley Hudson

Their research shows that fetal growth is adversely affected by decreased oxygen at high elevations in mice that are native to low elevations. Mice native to high elevations, however, have genetic differences that provide placental modifications that protect fetuses from hypoxia, which is a lack of oxygen to the fetus. This pattern is similar to that observed in humans, such as people of Tibetan or Andean ancestry. These human populations also protect fetal growth at high elevations, but researchers have little understanding of how it is achieved.

Cheviron said one of the most exciting aspects of their work was the discovery that many genes that seem to target fetal growth in their study species – highland deer mice – also have been associated with placental physiology in people.

“This suggests that the genetic and physiological mechanisms that underlie healthy pregnancies at high elevation may have deep evolutionary roots,” he said. “We might be able to use this insight to develop new treatments to improve pregnancy outcomes in humans.”

During the study, lowland mice experienced stunted fetal growth in hypoxia conditions, but highland mice avoided negative effects by altering their placentas.

“If we can understand how deer mice have ‘solved’ the problem of hypoxia for fetal growth,” Wilsterman said, “we may eventually be able to identify targets for treatment development in humans or be in a better position to identify where things are going wrong in gestational diseases that involve hypoxia.”

She said future studies will examine the tissue-level changes they discovered among deer mice. They also hope to identify the genetic variants that contribute to how specific cell types respond to hypoxia.

Reference: “Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice” by Kathryn Wilsterman, Emily C. Moore, Rena M. Schweizer, Kirksey Cunningham, Jeffrey M. Good and Zachary A. Cheviron, 12 June 2023, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2218049120

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