Epigenetic Regulation Interplays with Endometriosis Pathogenesis in Low-Birth-Weight Patients via the Progesterone Receptor B–VEGF-DNMT1 Axis

Abstract

Background: Low birth weight (LBW) is a risk factor associated with endometriosis. Our study aimed to analyze the risk of endometriosis in women with a LBW history and the relationships of progesterone receptor B (PR-B) gene promoter methylation, DNA methyltransferase-1 (DNMT1) expression, PR-B expression, and vascular endothelial growth factors (VEGF) with endometriosis. Methods: This study was conducted in two stages, a retrospective case-control design and a cross-sectional design, with 52 cases of endometriosis and 30 controls, which were further subdivided into LBW and non-LBW groups, at Hasan Sadikin General Hospital and its hospital networks from October 2017 to August 2021. Menstrual blood was taken from subjects and analyzed using pyrosequencing techniques to assess DNA methylation, while q-RT PCR was used to assess gene expression. Results: There were significant differences in PR-B methylation, DNMT1 expression, PR-B expression, and VEGF expression (p < 0.001) between the case and control groups. There was a significant negative correlation between PR-B methylation and PR-B expression (r = −0.558; p = 0.047). Based on a multiple logistic analysis, the most dominant factor affecting endometriosis incidence is PR-B (OR 10.40, 95% CI 3.24–33.4, R2 = 45.8). We found that patients with a low birth weight history had a 1.41-times-higher risk of developing endometriosis (95% CI 0.57–3.49, p = 0.113), although the relationship was not statistically significant. Conclusion: Endometriosis is associated with PR-B gene promoter hypermethylation, decreased PR-B expression, and increased DNMT1 and VEGF expression. The methylation of PR-B is the most dominant factor affecting endometriosis incidence.