Associations between maternal plasma concentrations of corticotrophin releasing hormone and the placental transcriptome.

Introduction: The placenta produces corticotrophin releasing hormone (CRH), which rises exponentially in maternal plasma across pregnancy. CRH plays a functional role in fetal development, labor initiation, and the regulation of gestational length. We aimed to understand how maternal plasma CRH during pregnancy reflects placental physiology during parturition by characterizing placental transcriptomic signatures of maternal plasma CRH and comparing to transcriptomic signatures of gestational age at birth.

Methods: Maternal plasma CRH concentrations were measured via radioimmunoassay at two timepoints and the placental transcriptome was quantified via RNA sequencing in 516 pregnant participants enrolled in the CANDLE cohort. Robust linear models were fitted to estimate associations between CRH and placental gene expression at birth. We conducted a functional validation in primary trophoblast cells before and after syncytialization.

Results: Plasma CRH concentrations in the mid-pregnancy visit were associated with placental expression of 8 differentially expressed genes (DEGs), and concentrations in late pregnancy were associated with 283 DEGs. These genes were involved in several metabolic pathways. Seven genes were significantly associated with both plasma CRH and gestational length. Four genes were concordantly decreased and 7 genes were concordantly increased in primary trophoblasts treated with CRH.

Discussion: Overall, this study reveals potential novel transcriptional mechanisms by which CRH may regulate metabolic pathways important for placental function and identifies genes associated with both CRH and gestational length.