Proliferative activity and expression of estrogen receptors in endometrial mesenchymal stromal cells in patients with repeated implantation failure

BACKGROUND: Endometrial receptivity disorders are the primary focus in patients with repeated implantation failure. However, the cellular and receptor characteristics of endometrial mesenchymal stromal cells in this population remain poorly understood, especially in terms of proliferative activity and estrogen receptor expression. This work examined the proliferative activity and expression of estrogen receptors in endometrial mesenchymal stromal cells in these patients to identify a new pathogenetic link of infertility and potential therapeutic targets. AIM: The work aimed to assess the functional characteristics of endometrial mesenchymal stromal cells, including their proliferative activity and estrogen receptor expression, in patients with repeated failure of euploid embryo implantation. METHODS: This pilot study included five patients aged 25–40 years. The main group included four patients with repeated implantation failure. An endometrial sample from a surrogate mother with a history of six term births served as a positive control. Mesenchymal stromal cells were isolated from endometrial aspiration biopsy samples collected during the first phase of the menstrual cycle. ESR1 expression was assessed by real-time polymerase chain reaction, and estrogen receptor alpha (ERα) levels were measured by fluorescent immunocytochemistry. The proliferative activity of mesenchymal stromal cells was assessed in the IncuCyte live-cell analysis system in a control medium and with 0.1 nM 17β-estradiol. RESULTS: ESR1 mRNA levels in cultured endometrial mesenchymal stromal cells were approximately 10 times higher than in adipose tissue mesenchymal stromal cells. Immunocytochemistry revealed specific expression of nuclear ERα in all samples. Patients with unexplained infertility had fewer receptors than the control group, with the lowest ERα expression reported in patients with tubal-peritoneal infertility. Endometrial mesenchymal stromal cells from patients with repeated implantation failure had a significantly lower proliferation rate than mesenchymal stromal cells from a surrogate mother. Patients with unexplained infertility had the lowest proliferative capacity of endometrial mesenchymal stromal cells. Adding 17β-estradiol significantly increased endometrial mesenchymal stromal cell proliferation in both the surrogate mother and patients with unexplained infertility. In patients with tubal-peritoneal infertility, 0.1 nM estradiol did not improve endometrial mesenchymal stromal cells proliferation. CONCLUSION: This work is the first to demonstrate decreased proliferative activity and expression of estrogen receptors (ERα) in endometrial mesenchymal stromal cells in patients with repeated implantation failure. The findings indicate that mesenchymal stromal cells from patients with unexplained infertility remain sensitive to estrogen despite the reduced number of receptors. These data add to a better understanding of the functional characteristics of endometrial mesenchymal stromal cells in repeated implantation failure.