Paquette Alison, Parenti Mariana, Lapehn Samantha, Konwar Chaini, Kadam Leena, Firsick Evan J, Barrett Emily S, MacIsaac Julie, MacDonald James, Bammler Theo, Carroll Kecia, Enquobahrie Daniel, Kobor Michael, LeWinn Kaja Z, Nguyen Ruby, Smith Roger, Spirzo Adam, Zhao Qi, Myatt Leslie, Bush Nicole R, Muglia Louis, Sathyanarayana Sheela
Seattle Children's Research Institute, Seattle WA, USA; University of Washington, Seattle WA, USA.
Seattle Children's Research Institute, Seattle WA, USA.
Placenta. 2025 Feb;160:29-38. doi: 10.1016/j.placenta.2024.12.021. Epub 2024 Dec 30.
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.
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.
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.
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.
胎盘会产生促肾上腺皮质激素释放激素（CRH），在整个孕期母体血浆中其水平呈指数上升。CRH在胎儿发育、分娩发动及孕期时长调节中发挥功能性作用。我们旨在通过描绘母体血浆CRH的胎盘转录组特征并与出生时胎龄的转录组特征进行比较，来了解孕期母体血浆CRH如何反映分娩时的胎盘生理状况。
在两个时间点通过放射免疫测定法测量516名参与CANDLE队列研究的孕妇的母体血浆CRH浓度，并通过RNA测序对胎盘转录组进行定量分析。采用稳健线性模型来估计CRH与出生时胎盘基因表达之间的关联。我们在合体化前后的原代滋养层细胞中进行了功能验证。
孕中期检查时的血浆CRH浓度与8个差异表达基因（DEG）的胎盘表达相关，孕晚期浓度与283个DEG相关。这些基因参与了多个代谢途径。7个基因与血浆CRH和孕期时长均显著相关。在用CRH处理的原代滋养层细胞中，4个基因一致下调，7个基因一致上调。
总体而言，本研究揭示了CRH可能调节对胎盘功能重要的代谢途径的潜在新转录机制，并确定了与CRH和孕期时长均相关的基因。
