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人绒毛膜促性腺激素通过增加同源盒 A10 的表达来提高子宫内膜的接受性。

Human chorionic gonadotropin improves endometrial receptivity by increasing the expression of homeobox A10.

机构信息

Reproductive Medicine Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, P.R. China.

出版信息

Mol Hum Reprod. 2020 Jun 1;26(6):413-424. doi: 10.1093/molehr/gaaa026.

Abstract

Homeobox A10 (HOXA10) is a characterized marker of endometrial receptivity. The mechanism by which hCG intrauterine infusion promotes embryo implantation is still unclear. This study seeks to investigate whether hCG improves endometrial receptivity by increasing expression of HOXA10. HOXA10 expression with human chorionic gonadotropin stimulation was analyzed in vitro and in vivo. Our results demonstrate that HOXA10 was decreased in the endometria of recurrent implantation failure patients compared to that in the healthy control fertile group, also we observed that hCG intrauterine infusion increased endometrial HOXA10 expression. HOXA10, blastocyst-like spheroid expansion area was increased, whereas DNA (cytosine-5-)-methyltransferase 1 was decreased when human endometrial stromal cells (hESCs) were treated with 0.2 IU/ml of hCG for 48 h. HOXA10 promoter methylation was also reduced after hCG treatment. Collagen XV (ColXV) can repress the expression of DNA (cytosine-5-)-methyltransferase 1, and hCG treatment increased the expression of ColXV. However, when the hESCs were treated with LH/hCG receptor small interfering RNA to knock down LH/hCG receptor, hCG treatment failed to repress DNA (cytosine-5-)-methyltransferase 1 expression or to increase ColXV expression. Our findings suggest that hCG may promote embryo implantation by increasing the expression of HOXA10.

摘要

Homeobox A10 (HOXA10) 是子宫内膜容受性的特征性标志物。人绒毛膜促性腺激素(hCG)宫腔内注射促进胚胎着床的机制尚不清楚。本研究旨在探讨 hCG 是否通过增加 HOXA10 的表达来提高子宫内膜容受性。在体外和体内分析了 hCG 刺激对 HOXA10 表达的影响。结果表明,与健康对照组相比,复发性着床失败患者的子宫内膜中 HOXA10 表达降低,并且我们观察到 hCG 宫腔内注射增加了子宫内膜 HOXA10 的表达。当人子宫内膜基质细胞(hESCs)用 0.2 IU/ml 的 hCG 处理 48 小时时,HOXA10 启动子甲基化也减少。胶原 XV(ColXV)可以抑制 DNA(胞嘧啶-5-)-甲基转移酶 1 的表达,而 hCG 处理增加了 ColXV 的表达。然而,当 hESCs 用 LH/hCG 受体小干扰 RNA 处理以敲低 LH/hCG 受体时,hCG 处理未能抑制 DNA(胞嘧啶-5-)-甲基转移酶 1 的表达或增加 ColXV 的表达。我们的研究结果表明,hCG 可能通过增加 HOXA10 的表达来促进胚胎着床。

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