Grbac Eliza, So Teresa, Varshney Swati, Williamson Nicholas, Dimitriadis Evdokia, Menkhorst Ellen
Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC, Australia.
Gynaecology Research Centre, Royal Women's Hospital, Parkville, VIC, Australia.
Front Cell Dev Biol. 2021 Apr 9;9:647496. doi: 10.3389/fcell.2021.647496. eCollection 2021.
Poor pregnancy outcomes such as recurrent pregnancy loss (RPL) and preeclampsia are associated with impaired decidualization and abnormal trophoblast invasion. Emerging evidence suggests that use of corticosteroids, including prednisolone affects fertility by altering uterine function and may be associated with preeclampsia incidence. In this study, using primary and gestational-age appropriate tissue, we aimed to define the effect of prednisolone on human endometrial stromal fibroblast (hESF) decidualization and determine whether hESF decidualization in the presence of prednisolone would alter hESF regulation of trophoblast function. We found that prednisolone treatment reduced hESF cytokine expression (, , , and ) but had no effect on hESF expression or secretion of the classic markers of decidualization [prolactin (PRL) and IGFBP1]. Using proteomics we determined that prednisolone altered decidualized hESF protein production, enriching hESF proteins associated with acetylation and mitrochondria. Conditioned media from hESF decidualized in the presence of prednisolone significantly enhanced trophoblast outgrowth and trophoblast mRNA expression of cell motility gene and reduced trophoblast production of . Prednisolone treatment during the menstrual cycle and 1st trimester of pregnancy might alter decidual interactions with other cells, including invasive trophoblast.
复发性流产（RPL）和先兆子痫等不良妊娠结局与蜕膜化受损和滋养层细胞异常侵袭有关。新出现的证据表明，包括泼尼松龙在内的皮质类固醇的使用会通过改变子宫功能影响生育能力，并且可能与先兆子痫的发生率有关。在本研究中，我们使用原代且适合孕龄的组织，旨在确定泼尼松龙对人子宫内膜基质成纤维细胞（hESF）蜕膜化的影响，并确定在泼尼松龙存在的情况下hESF蜕膜化是否会改变hESF对滋养层细胞功能的调节。我们发现，泼尼松龙处理降低了hESF细胞因子的表达（、、和），但对hESF蜕膜化的经典标志物[催乳素（PRL）和胰岛素样生长因子结合蛋白1（IGFBP1）]的表达或分泌没有影响。通过蛋白质组学我们确定，泼尼松龙改变了蜕膜化hESF的蛋白质产生，使与乙酰化和线粒体相关的hESF蛋白质富集。在泼尼松龙存在的情况下蜕膜化的hESF的条件培养基显著增强了滋养层细胞的生长以及细胞运动基因的滋养层细胞mRNA表达，并减少了的滋养层细胞产生。在月经周期和妊娠早期进行泼尼松龙治疗可能会改变蜕膜与其他细胞（包括侵袭性滋养层细胞）之间的相互作用。
