Estrogen-sensitive activation of SGK1 induces M2 macrophages with anti-inflammatory properties and a Th2 response at the maternal–fetal interface

作者：Yiyun Lou, Zhujing Fu, Ye Tian, Minhao Hu, Qijing Wang, Yuanyuan Zhou, Ning Wang, Qin Zhang, Fan Jin · 发表于：Reproductive Biology and Endocrinology · 年份：2023 · DOI：10.1186/s12958-023-01102-9 · 被引用次数：28 · 研究领域：Reproductive System and Pregnancy、Pregnancy and preeclampsia studies、Pregnancy and Medication Impact

Abstract Background Decidual macrophages participate in immune regulation at the maternal–fetal interface. Abnormal M1/M2 polarization of decidual macrophages might predispose immune maladaptation in recurrent pregnancy loss (RPL). However, the mechanism of decidual macrophage polarization is unclear. We explored the role of Estradiol (E 2 )-sensitive serum-glucocorticoid regulated kinase (SGK) 1 in promoting macrophage polarization and suppressing inflammation at the maternal–fetal interface. Methods We assessed serum levels of E 2 and progesterone during first trimester of pregnancy in women with or without threatened miscarriages (ended in live birth, n = 448; or early miscarriages, n = 68). For detection of SGK1 in decidual macrophages, we performed immunofluorescence labeling and western blot analysis applying decidual samples from RPL ( n = 93) and early normal pregnancy ( n = 66). Human monocytic THP-1 cells were differentiated into macrophages and treated with Toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), E 2 , inhibitors or siRNA for in vitro analysis. Flow cytometry analysis were conducted to detect macrophages polarization. We also applied ovariectomized (OVX) mice with hormones exploring the mechanisms underlying the regulation of SGK1 activation by E 2 in the decidual macrophages in vivo. Results SGK1 expression down regulation in the decidual macrophages of RPL was consistent with the lower concentration and slower increment of serum E 2 from 4 to ...