Exposure to lipopolysaccharide induces sexually dimorphic placental adaptation by modifying placental efficiency, morphogenesis, and gene expression

Sexual dimorphism in placental physiology during development affects the functionality of placental adaptation during adverse pregnancy, affecting fetal growth, development, and eventually fetal programming, which have long-term effects on the offspring's adult life. However, studies focusing on the phenomenon and relationship between sex-specific placental adaptation and consequent altered fetal development are still elusive. Here, we established a prenatal maternal stress model by administering lipopolysaccharide (LPS) to pregnant ICR mice at the mid-gestational stage. To verify the appropriateness of the animal model to study sex differences in the sub-optimal uterus milieu, pregnancy complications were examined. To elucidate global transcriptomic changes occurring in the placenta, total RNA sequencing was performed in female and male placentas. LPS exposure at the mid-gestational stage induced placental inflammation in both sexes. In utero inflammatory conditions resulted in intrauterine fetal growth restriction and impaired placental development in a sex-specific manner depending on the dose of LPS. Sex-biased placental pathology was observed in the junctional zone and the labyrinth layer. Placental transcriptome analysis revealed widespread disparity in protein-coding and long non-coding genes between female and male placentas, presenting the relationship between morphology and function in a sex-specific IUGR model. Overall design: Female and male placentas were isolated from pregnant ICR mice treated with 200 ml of PBS or LPS (400 mg/kg) at gestational day 15.5 for 48 hrs. For individual sample, we pooled 6-8 placentas from 3 different pregnant mice. For each group we have 2 biological replicates in PBS and 3 biological replicates in LPS. The total number of samples is 10.