Bioinformatics-based analysis of the roles of sex hormone receptors in endometriosis development

Abstract

Endometriosis is a hormone-dependent disease in women of reproductive age and seriously affects women's health. To analyze the involvement of sex hormone receptors in endometriosis development, we performed bioinformatics analysis using four datasets derived from the Gene Expression Omnibus (GEO) database, which may help us understand the mechanisms by which the sex hormones act in vivo in endometriosis patients. The enrichment analysis and protein-protein interaction (PPI) analysis of the differentially expressed genes (DEGs) revealed that there are different key genes and pathways involved in eutopic endometrium aberrations of endometriosis patients and endometriotic lesions, and sex hormone receptors, including androgen receptor (AR), progesterone receptor (PGR) and estrogen receptor 1 (ESR1), may play important roles in endometriosis development. Androgen receptor (AR), as the hub gene of endometrial aberrations in endometriotic patients, showed positive expression in the main cell types for endometriosis development, and its decreased expression in the endometrium of endometriotic patients was also confirmed by immunohistochemistry (IHC). The nomogram model established based on it displayed good predictive value.

Systemic Effect of Human Follicular Fluid from Endometriotic and Healthy Subjects on Female Mice

“…Obesity and abdominal obesity are linked to higher levels of blood androgens and luteinizing hormone, which exacerbates the clinical traits of infertility and monthly irregularity. 22 Hence, the etiology and pathophysiology of endometriosis are influenced by a complicated interaction between body mass index, abdominal obesity, insulin resistance, androgen level, and LH level. 23 Results of our study endorses these outcomes as we have seen the higher level of serum testosterone upon 21 days treatment with endometriotic fluid.…”

Recent insights explaining susceptibility to endometriosis—From genetics to environment

“…Androgens target fibroblasts cells in normal endometrium. In endometriosis, activation of androgen receptors is suggested for the development of the disease, mainly with greater density in stromal cells and in pelvic lesions, but with decrease expression in endometrium (Massarotti et al, 2021; X. Zhao et al, 2023). Androgen receptor polymorphism can contribute to the pathogenesis of endometriosis and the most studied are the cytosine, adenine, and guanine (CAG) repeat polymorphisms (Fujimoto et al, 1999; Lattuada et al, 2004; Noor Ahmad Shaik et al, 2009; Osiński et al, 2018; Shin et al, 2017).…”

“…Androgens target fibroblasts cells in normal endometrium. In endometriosis, activation of androgen receptors is suggested for the development of the disease, mainly with greater density in stromal cells and in pelvic lesions, but with decrease expression in endometrium (Massarotti et al, 2021;X. Zhao et al, 2023).…”