Padrão de metilação das regiões controladoras de imprinting genômico, H19DMR E KvDMR1, em mulheres com endometriose

Abstract

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial tissue outside the uterine cavity, affecting approximately 10% of women of reproductive age. The clinical manifestations are diverse and the origin of endometriosis remains unclear. However, the disease is believed to be multifactorial, with epigenetic components playing a significant role. Genomic imprinting regulates key cellular physiological functions, and its disruption can lead to aberrant gene activation, resulting in epigenetic reprogramming errors. In this study, we evaluated the methylation pattern of the H19DMR and KvDMR1 regions using bisulfite sequencing, as well as the expression levels of lncRNA H19 and KCNQ1OT1 by RT-qPCR of 24 pelvic lesions collected through videolaparoscopy. Among the results obtained, the mean age of participants was 33.5 years. The rectovaginal septum was the most frequent lesion site (66.7%) and dysmenorrhea was the most commoly reported symptom. The average methylation levels were 42.98% ± 5.38% for H19DMR and 58.79% ± 4.74% for KvDMR1. No statistically significant differences in methylation or lncRNA expression were observed across disease classifications. However, three cases of hypomethylation in H19DMR and two cases of hypermethylation in KvDMR1 were identified in infiltrative lesions. Additionally, a predominance of the heterozygous pattern was observed in the rs2107425 (C/T = 53.3%) and rs2071094 (G/T = 66.6%) regions. Notably, a significant association was found between H19 expression and family history of endometriosis (p = 0.0469), along with a negative correlation between H19 expression and BMI (p = 0.035, r = - 0.498). These findings underscore the importance of further investigating epigenetic mechanisms in endometriosis, as they may contribute to disease progression and its clinical heterogeneity.