# Conserved gene expression patterns in the placenta underlie pregnancy complications associated with hypoxia in mice and humans

## TL;DR

This study shows that hypoxia during pregnancy affects placental gene activity in mice and humans, potentially causing fetal growth issues.

## Contribution

The study identifies conserved gene expression patterns in mouse and human placentas under hypoxia, linking them to pregnancy complications.

## Key findings

- Hypoxia alters placental gene expression related to calcium binding, lipid metabolism, and PPAR signaling in mice.
- Placental nutrient transport and fetal weight are reduced in a severity-dependent manner due to hypoxia.
- Key hypoxia-responsive genes in mice are associated with human pregnancy outcomes, suggesting conserved mechanisms.

## Abstract

During pregnancy hypoxia leads to complications like fetal growth restriction (FGR). Maternal inhalation hypoxia during late murine pregnancy impairs placental phenotype and fetal development in a severity-dependent manner. To identify the molecular mechanisms and sex-specificity of these effects, placentas from pregnant mice exposed to moderate (13% O₂) or severe (10% O₂) hypoxia were analysed using RNA-sequencing, qPCR, western blotting, histology, and nutrient transport assays. Transcriptomic profiling of male 13% O2 placentas revealed differential gene expression regulating calcium binding, lipid metabolism, and peroxisome proliferator-activated receptor (PPAR) signalling. In both sexes, hypoxia reduced fetal weight and altered placental nutrient transport in a severity-dependent manner. Abundance of PPARα, PPARγ, and associated targets varied with sex and hypoxia severity. Placental calcium deposition was significantly increased by hypoxia irrespective of severity. Human placental datasets revealed that orthologues of key hypoxia-responsive genes in the mouse placenta are also associated with pregnancy outcomes in human pregnancy. These findings implicate placental PPAR signalling and calcium dysregulation as potential mediators of FGR in compromised pregnancies.

The online version contains supplementary material available at 10.1007/s00018-026-06110-7.