JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):154
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263935

P-142. In Silico Analysis of Testosterone-Mediated Gene Regulation in the Endometrium of Women with Polycystic Ovary Syndrome

Paula Barros Terraciano¹, Marília Felisberti Benites², Rafaela Ferreira-Da-Silva², Giovanna Camara Giudicelli¹, Markus Berger¹, Eduardo Pandolfi Passos³, Maríndia Deprá²

¹ Hospital de Clínicas de Porto Alegre - Porto Alegre - Rio Grande do Sul – Brasil
² Universidade Federal do Rio Grande do Sul - Porto Alegre - Rio Grande do Sul - Brasil
³ Hospital Moinhos de Vento - Porto Alegre - Rio Grande do Sul – Brasil

Objective: Infertility is diagnosed after one year of unsuccessful attempts to conceive and is associated with substantial physical and emotional impact. Common causes include tubal obstruction, endometriosis, hormonal and ovulatory disorders, and implantation failures. Implantation requires the penetration of the blastocyst into the maternal endometrium, a process dependent on a receptive uterine environment. In polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenism, irregular menstrual cycles, and polycystic ovarian morphology, hormonal alterations—particularly elevated testosterone—can disrupt the expression of genes critical for implantation. Among these, HOX family genes, such as HOXA10, play essential roles in endometrial receptivity. Previous studies indicate an inverse relationship between testosterone levels and HOX gene expression, suggesting that hyperandrogenism may contribute to reduced pregnancy rates in PCOS. This study aimed to evaluate, through in silico analysis, the potential regulatory effects of testosterone on HOX gene expression in the endometrium.
Methods: A publicly available RNA-sequencing dataset was analyzed to investigate differential gene expression in endometrial tissue under varying testosterone conditions. Bioinformatic tools were applied to identify genes with statistically significant upregulation or downregulation. Analyses focused on HOX family members but also considered other genes with relevant changes. Fold-change thresholds and adjusted p-values were used to classify expression differences.
Results: Contrary to our initial hypothesis, no HOX family members were identified as significantly upregulated or downregulated in the dataset analyzed. However, other genes exhibited marked expression changes. Among the most strongly downregulated were FLG, ZNF418, DMRTA1, and GIMAP7, while highly upregulated genes included ZFP37, L3MBTL, and ZNF711. Notably, CDKN2C, encoding the p18^INK4C protein, was also upregulated. This protein functions as an inhibitor of cyclin-dependent kinases CDK4 and CDK6, which, in complex with cyclin D, regulate cell cycle progression by preventing phosphorylation of key cellular targets. The altered expression of CDKN2C and other non-HOX genes may indicate indirect pathways through which testosterone affects endometrial cell function and receptivity.
Conclusion: In this in silico analysis, no significant alterations in HOX gene expression were detected, possibly due to dataset limitations, including sample size. Nonetheless, several non-HOX genes with potential relevance to endometrial physiology were differentially expressed, including those involved in epithelial integrity, transcriptional regulation, and cell cycle control. These findings suggest that testosterone may influence endometrial receptivity through alternative molecular pathways beyond direct HOX gene regulation. Further studies with larger and more diverse datasets are necessary to validate these observations and clarify the role of androgen-mediated gene regulation in the implantation process of women with PCOS.