Endocrine-disrupting chemicals and epigenetic reprogramming in developmental origin of uterine fibroids

Abstract

Endocrine-disrupting chemicals (EDCs) are a class of exogenous substances that mimic the effects of hormones in the body, inducing hormonal dysregulation and contributing to various disorders. Epigenome regulation has emerged as an important mechanism for maintaining organ function in health and disease. Dissecting epigenomic and resultant gene expression changes provides unprecedented insight into the chromatin state, which underlines disease development and shapes risk and phenotypic plasticity in response to the environment and internal cues. The cutting-edge, high throughput technologies provide new routes to understanding the etiology of disease and new footholds on the promising path to better treatment and disease prevention. We have recently revealed that myometrial stem cells (MMSCs), the cell origin of UFs, are the target of developmental EDC exposure. The EDC-induced epigenetic changes in MMSCs identified by multi-omics approaches include DNA methylation and histone modification modulated by DNA methyltransferases and MLL1, which characterized the molecular mechanism underlying EDC-related risk in hormone-dependent UFs. Future studies are needed to determine the link between real-life exposures to EDCs and their impact on the development of human diseases and transgenerational epigenetic inheritance, which can help explore strategies that may prevent adverse outcomes linked to EDC exposure.

Comprehensive Review of Uterine Leiomyosarcoma: Pathogenesis, Diagnosis, Prognosis, and Targeted Therapy

“…They arise from the smooth muscle wall of the uterus [40]. It is hypothesized and demonstrated that LMs originate from the abnormal stem cells of the myometrium [41][42][43][44]. However, the specific cell of origin has yet to be identified [45].…”