子宫内膜容受性不足通常会导致胚胎着床失败和流产。人绒毛膜促性腺激素(hCG)是早期胚胎发育过程中分泌的关键信号分子。它调节胚胎母体界面信号并促进胚胎植入。本研究旨在探讨hCG对子宫内膜容受性的影响及其潜在机制。设计了一项探索性研究,和子宫内膜样本是从诊断为单纯性输卵管不育或男性因素不育(n=12)和复发性植入失败(RIF,n=10)。使用逆转录定量PCR和蛋白质印迹,检测子宫内膜组织中黄体生成素(LH)/hCG受体(LHCGR)水平和自噬。随后,从这些对照组中分离出原代子宫内膜基质细胞(ESC),并用hCG处理以检查LHCGR的存在和子宫内膜容受性标志物(HOXA10,ITGB3,FOXO1,LIF,和L-选择素配体)和自噬相关因子(Beclin1,LC3和P62)。研究结果表明,接受性因子的表达,LHCGR,与对照组相比,RIF妇女的子宫内膜组织中LC3减少,而P62的表达升高。HCG对ESC的给药特异性激活LHCGR,刺激子宫内膜产生HOXA10,ITGB3,FOXO1,LIF和L-选择素配体的增加。此外,当ESC暴露于0.1IU/mLhCG72小时时,细胞内自噬因子Beclin1和LC3增加,P62减少。此外,凋亡因子Bax增加,Bcl-2下降。然而,当使用小干扰RNA来敲低LHCGR时,hCG对子宫内膜容受性和自噬分子的控制能力较弱。此外,hCG刺激增强了ERK1/2和mTOR蛋白的磷酸化。这些结果表明,患有RIF的女性在子宫内膜组织中表现出较低水平的LHCGR和受损的自噬功能。因此,hCG/LHCGR可能通过调节自噬和凋亡而改善子宫内膜容受性。
Inadequate endometrial receptivity often results in embryo implantation failure and miscarriage. Human chorionic gonadotropin (hCG) is a key signaling molecule secreted during early embryonic development, which regulates embryonic maternal interface signaling and promotes embryo implantation. This study aimed to examine the impact of hCG on endometrial receptivity and its underlying mechanisms. An exploratory study was designed, and endometrial samples were obtained from women diagnosed with simple tubal infertility or male factor infertile (n = 12) and recurrent implantation failure (RIF, n = 10). Using reverse transcription-quantitative PCR and western blotting, luteinizing hormone (LH)/hCG receptor (LHCGR) levels and autophagy were detected in the endometrial tissues. Subsequently, primary endometrial stromal cells (ESCs) were isolated from these control groups and treated with hCG to examine the presence of LHCGR and markers of endometrial receptivity (HOXA10, ITGB3, FOXO1, LIF, and L-selectin ligand) and autophagy-related factors (Beclin1, LC3, and P62). The findings revealed that the expressions of receptivity factors, LHCGR, and LC3 were reduced in the endometrial tissues of women with RIF compared with the control group, whereas the expression of P62 was elevated. The administration of hCG to ESCs specifically activated LHCGR, stimulating an increase in the endometrial production of HOXA10, ITGB3, FOXO1, LIF and L-selectin ligands. Furthermore, when ESCs were exposed to 0.1 IU/mL hCG for 72 h, the autophagy factors Beclin1 and LC3 increased within the cells and P62 decreased. Moreover, the apoptotic factor Bax increased and Bcl-2 declined. However, when small interfering RNA was used to knock down LHCGR, hCG was less capable of controlling endometrial receptivity and autophagy molecules in ESCs. In addition, hCG stimulation enhanced the phosphorylation of ERK1/2 and mTOR proteins. These results suggest that women with RIF exhibit lower levels of LHCGR and compromised autophagy function in their endometrial tissues. Thus, hCG/LHCGR could potentially improve endometrial receptivity by modulating autophagy and apoptosis.