Heat Stress-Induced Fetal Intrauterine Growth Restriction Is Associated with Elevated LPS Levels Along the Maternal Intestine-Placenta-Fetus Axis in Pregnant Mice.

ABSTRACT

The exacerbation of the greenhouse effect has made heat stress (HS) an important risk factor for the occurrence of intrauterine growth restriction (IUGR). The experiment aims to uncover the effects of maternal HS on IUGR and its mechanisms. The results showed that HS leads to decreased maternal and fetal birth weights, accompanied by increased serum oxidative stress and cortisol levels. Moreover, HS inflicted significant damage to both the intestinal and placental barriers, altering maternal gut microbiota and increasing intestinal LPS levels. As a result, LPS levels increased in maternal serum, placenta, and fetus. Furthermore, HS damaged the intestinal structure, intensifying inflammation and disrupting the redox balance. The placenta exposed to HS exhibited changes in the placental structure along with disrupted angiogenesis and decreased levels of nutritional transporters. Additionally, the leakage of LPS triggered placental JNK and ERK phosphorylation, ultimately inducing severe placental inflammation and oxidative stress. This study suggests that LPS translocation from the maternal intestine to the fetus, due to a disrupted gut microbiota balance and compromised intestinal and placental barrier integrity, may be the primary cause of HS-induced IUGR. Furthermore, increased LPS leakage leads to placental inflammation, redox imbalance, and impaired nutrient transport, further restricting fetal growth.