JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):130
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263765

P-118. Hormonal Regulation of HOXA11 Expression, Viability, and Migration in Human Endometrial Mesenchymal Cells: Implications for Endometrial Receptivity in Polycystic Ovary Syndrome

Isabel Oliveira Durli¹, Markus Berger¹, Maria Eduarda Leite Simões¹, Amanda Wink Santos¹, Lívia Cardoso Oliveira¹, Ivan Sereno Montenegro¹, Eduardo Pandolfi Passos², Paula Barros Terraciano¹

¹ Hospital de Clínicas de Porto Alegre - Porto Alegre - RS – Brasil
² Hospital Moinhos de Vento - Porto Alegre - RS – Brasil

Objective: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, frequently associated with infertility. One mechanism by which PCOS impairs fertility is through altered endometrial receptivity, which compromises embryo implantation. Endometrial remodeling during the menstrual cycle is regulated by ovarian steroid hormones and leads to the formation of the decidua—a specialized tissue essential for implantation. In PCOS, hormonal imbalances may disrupt this process. HOX family genes, particularly HOXA11, are critical for endometrial development, regulating stromal decidualization, pinopode formation, and embryo nourishment during the implantation window. Their expression is modulated by estrogen and progesterone. This study aimed to evaluate whether elevated levels of testosterone, progesterone, and their combination affect HOXA11 expression, cell viability, and migration in human endometrial mesenchymal cells.
Methods: Human endometrial mesenchymal cells were cultured and treated for 24 hours with testosterone, progesterone, or a combination of both hormones. Three assays were performed to assess cellular responses: (1) Western blotting to quantify HOXA11 protein expression; (2) MTT assay to determine cell viability; and (3) wound healing assay to evaluate migratory capacity. Control groups received vehicle treatment under identical conditions. All experiments were conducted in triplicate, and data were analyzed for statistically significant differences between treatment groups.
Results: Western blot analysis revealed a marked increase in HOXA11 expression in cells treated with the combination of progesterone and testosterone compared with the control group. Progesterone alone induced a moderate upregulation, whereas testosterone alone had minimal effect on HOXA11 levels. In the wound healing assay, progesterone treatment significantly accelerated wound closure compared with all other groups, indicating enhanced cell migration. Testosterone alone did not improve migration, while the combination treatment resulted in an intermediate effect between progesterone alone and control. In the MTT assay, both progesterone and the progesterone-plus-testosterone treatments increased cell viability compared with control and testosterone-only groups. The viability of cells treated with progesterone alone was comparable to that of the combination group, suggesting a predominant role of progesterone in promoting cell survival.
Conclusion: Progesterone plays a central role in enhancing HOXA11 expression, cell viability, and migration in human endometrial mesenchymal cells, with testosterone showing a synergistic effect on HOXA11 expression when combined with progesterone. These findings suggest that adequate progesterone signaling is essential for optimizing endometrial receptivity and that specific hormonal imbalances in PCOS may impair implantation by disrupting HOXA11-mediated endometrial remodeling. Understanding these molecular interactions could inform targeted therapies to improve fertility outcomes in women with PCOS.