Heat Exposure in Pregnancy Induces Fetal Growth Restriction via Placental Hypoxia in Mice

Abstract

Extreme heat events have become increasingly frequent with global climate change, posing significant threats to maternal and fetal health. Although epidemiological studies have suggested associations between maternal heat exposure during pregnancy and adverse birth outcomes, direct experimental evidence on how heat exposure leads to fetal growth restriction (FGR) and the underlying mechanisms is still lacking.This study used a mouse model to explore the impact pathway of maternal heat exposure leading to FGR with a focus on the placenta. Female CD1 mice were divided into a room temperature group (25°C) and a heat exposure group (40°C, 50% humidity, 2 hours daily throughout pregnancy). Placenta and fetal samples were collected, and weights were recorded at key gestational stages at embryonic day 7.5 (E7.5), E10.5, E13.5, E16.5, and E18.5. Maternal heat exposure significantly decreased placental efficiency and fetal weight at E13.5 and E16.5, and lower birth weight on postnatal day 1 (PND1) (p<0.05) compared to the control group. Using photoacoustic imaging technology (PAM), we dynamically monitored placental blood oxygen saturation (sO₂), blood perfusion, and vessel diameter before and after heating (40°C, 30 minutes). The results showed that heat exposure significantly reduced placental blood oxygen saturation, blood perfusion, and vessel diameter across all gestational stages. The study recapitulated well-established adverse birth outcomes associated with maternal heat exposure, including fetal growth restriction and low birth weight, validating the model’s translational relevance. Our study further revealed an underlying mechanism of this association through placental hypoxia. These findings highlight the importance of incorporating heat exposure risks into maternal health management and advancing climate-adaptive strategies in clinical and public health settings.