Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
Department of Animal Science, College of Natural Resources, Michigan State University, East Lansing, MI, USA.
Am J Reprod Immunol. 2017 Nov;78(5). doi: 10.1111/aji.12741. Epub 2017 Aug 28.
Heightened maternal stress affects trophoblast function and increases risk for adverse pregnancy outcomes.
Studies were performed using the first-trimester trophoblast cell line, Sw.71. Cytokines were quantified using qPCR and ELISA. Epigenetic regulation of cytokines was characterized by inhibiting histone deacetylation (1 μmol/L suberoylanilide hydroxamic acid [SAHA]) or methylation (5 μmol/L 5-azacytidine), or with chromatin immunoprecipitation (ChIP) with a pan-acetyl histone-3 antibody. Invasion assays used Matrigel chambers.
Cortisol inhibited expression of CSF2 (GM-CSF) and CSF3 (G-CSF) in trophoblast cells. Cortisol-associated inhibition was dependent on DNA methylation and was not affected by acetylation. There was also a modest decrease in trophoblast invasion, not dependent on loss of CSFs.
In first-trimester trophoblast cells, the physiological glucocorticoid, cortisol, inhibited two cytokines with roles in placental development and decreased trophoblast invasion. Cortisol-associated changes in trophoblast function could increase the risk for immune-mediated abortion or other adverse pregnancy outcomes.
母体应激增加会影响滋养层功能，增加不良妊娠结局的风险。
使用第一孕期滋养层细胞系 Sw.71 进行研究。采用 qPCR 和 ELISA 定量检测细胞因子。通过抑制组蛋白去乙酰化（1 μmol/L 丁氧羰基邻氨基苯甲酸[SAHA]）或甲基化（5 μmol/L 5-氮杂胞嘧啶），或用泛乙酰化组蛋白-3 抗体进行染色质免疫沉淀（ChIP），对细胞因子的表观遗传调控进行了表征。侵袭实验使用 Matrigel 室。
皮质醇抑制滋养层细胞中 CSF2（GM-CSF）和 CSF3（G-CSF）的表达。皮质醇相关的抑制作用依赖于 DNA 甲基化，不受乙酰化的影响。滋养层细胞的侵袭能力也略有下降，但与 CSFs 的缺失无关。
在第一孕期的滋养层细胞中，生理性糖皮质激素皮质醇抑制了两种在胎盘发育中起作用的细胞因子，并降低了滋养层细胞的侵袭能力。皮质醇相关的滋养层功能变化可能会增加免疫介导性流产或其他不良妊娠结局的风险。
