Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services (NICHD/NIH/DHHS), Detroit, MI, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Reprod Sci. 2021 Aug;28(8):2246-2260. doi: 10.1007/s43032-020-00454-6. Epub 2021 Mar 1.
Human chorionic gonadotropin (hCG) is a critical hormone for the establishment and maintenance of pregnancy. hCG administration prevents the onset of preterm labor in mice; yet, the transcriptomic changes associated with this tocolytic effect that take place in the myometrium and cervix have not been elucidated. Herein, we implemented both discovery and targeted approaches to investigate the transcriptome of the myometrium and cervix after hCG administration. Pregnant mice were intraperitoneally injected with 10 IU of hCG on 13.0, 15.0, and 17.0 days post coitum, and the myometrium and cervix were collected. RNA sequencing was performed to determine differentially expressed genes, enriched biological processes, and impacted KEGG pathways. Multiplex qRT-PCR was performed to investigate the expression of targeted contractility- and inflammation-associated transcripts. hCG administration caused the differential expression of 720 genes in the myometrium. Among the downregulated genes, enriched biological processes were primarily associated with regulation of transcription. hCG administration downregulated key contractility genes, Gja1 and Oxtr, but upregulated the prostaglandin-related genes Ptgfr and Ptgs2 and altered the expression of inflammation-related genes in the myometrium. In the cervix, hCG administration caused differential expression of 3348 genes that were related to inflammation and host defense, among others. The downregulation of key contractility genes and upregulation of prostaglandin-related genes were also observed in the cervix. Thus, hCG exerts tocolytic and immunomodulatory effects in late gestation by altering biological processes in the myometrium and cervix, which should be taken into account when considering hCG as a potential treatment to prevent the premature onset of labor.
人绒毛膜促性腺激素（hCG）是妊娠建立和维持的关键激素。hCG 给药可预防小鼠早产；然而，hCG 这种保胎作用在子宫肌层和宫颈中相关的转录组变化尚未阐明。在此，我们采用发现和靶向方法研究了 hCG 给药后子宫肌层和宫颈的转录组。在妊娠 13.0、15.0 和 17.0 天，通过腹腔内注射 10IU 的 hCG 处理怀孕小鼠，并收集子宫肌层和宫颈。进行 RNA 测序以确定差异表达基因、富集的生物学过程和受影响的 KEGG 途径。进行多重 qRT-PCR 以研究靶向收缩和炎症相关转录物的表达。hCG 给药导致子宫肌层中 720 个基因的差异表达。下调基因中，富集的生物学过程主要与转录调控相关。hCG 给药下调了关键收缩基因 Gja1 和 Oxtr，但上调了前列腺素相关基因 Ptgfr 和 Ptgs2，并改变了子宫肌层中炎症相关基因的表达。在宫颈中，hCG 给药导致 3348 个基因的差异表达，这些基因与炎症和宿主防御等有关。关键收缩基因的下调和前列腺素相关基因的上调也在宫颈中观察到。因此，hCG 通过改变子宫肌层和宫颈中的生物学过程发挥保胎和免疫调节作用，在考虑 hCG 作为预防早产的潜在治疗方法时应考虑到这一点。
