Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, China.
Department of Obstetrics and Gynecology, The First Hospital Affiliated Soochow University, Suzhou 215000, China.
Biol Reprod. 2021 May 7;104(5):1034-1044. doi: 10.1093/biolre/ioab017.
Differentiation of endometrial stromal cells (ESCs) into secretory decidualized cells (dESCs) is essential for embryo implantation. Adenomyosis is a common benign gynecological disease that causes infertility. However, whether adenomyosis affects decidualization of human ESCs is elusive. Primary eutopic ESCs were obtained from patients with adenomyosis (n = 9) and women with nonendometrial diseases (n = 12). We determined the capacity of decidualization of human ESCs by qRT-PCR, Edu proliferation assay, cytokine array, and ELISA assay. We found that the expression of decidualization markers (IGFBP1 and PRL) in ESCs of adenomyosis was reduced, concomitant with increased cell proliferation. Differential secretion of cytokines in dESCs, including CXCL1/2/3, IL-6, IL-8, MCP-1, VEGF-A, MIP-3α, OPN, SDF-1α, HGF, and MMP-9, was observed between adenomyosis and nonadenomyosis. Moreover, the expression of decidualization regulators (HOXA10 at both mRNA and protein levels, FOXO1, KLF5, CEBPB, and HAND2 at mRNA levels) in the eutopic endometrium of adenomyosis was lower than that of nonadenomyosis. We propose that ESCs from adenomyosis have defected ability to full decidualization, which may lead to a nonreceptive endometrium.
子宫内膜基质细胞(ESCs)向分泌性蜕膜化细胞(dESCs)的分化对于胚胎着床至关重要。子宫腺肌病是一种常见的良性妇科疾病,可导致不孕。然而,子宫腺肌病是否影响人 ESC 的蜕膜化仍不清楚。我们从患有子宫腺肌病的患者(n=9)和非子宫内膜疾病的妇女(n=12)中获得了原发性在位 ESCs。我们通过 qRT-PCR、Edu 增殖测定、细胞因子阵列和 ELISA 测定来确定人 ESC 蜕膜化的能力。我们发现,子宫腺肌病 ESC 中蜕膜化标志物(IGFBP1 和 PRL)的表达减少,同时细胞增殖增加。在 dESCs 中观察到细胞因子的差异分泌,包括 CXCL1/2/3、IL-6、IL-8、MCP-1、VEGF-A、MIP-3α、OPN、SDF-1α、HGF 和 MMP-9,在子宫腺肌病和非子宫腺肌病之间存在差异。此外,子宫腺肌病在位子宫内膜中蜕膜化调节因子(HOXA10 在 mRNA 和蛋白质水平、FOXO1、KLF5、CEBPB 和 HAND2 在 mRNA 水平)的表达低于非子宫腺肌病。我们提出,来自子宫腺肌病的 ESC 具有缺陷的完全蜕膜化能力,这可能导致子宫内膜无反应。