Endocrine disruptor exposure during development increases incidence of uterine fibroids by altering DNA repair in myometrial stem cells.

ABSTRACT: Despite the major negative impact uterine fibroids (UFs) have on female reproductive health, little is known about early events that initiate development of these tumors. Somatic fibroid-causing mutations in mediator complex subunit 12 (MED12), the most frequent genetic alterations in UFs (up to 85% of tumors), are implicated in transforming normal myometrial stem cells (MSCs) into tumor-forming cells, though the underlying mechanism(s) leading to these mutations remains unknown. It is well accepted that defective DNA repair increases the risk of acquiring tumor-driving mutations, though defects in DNA repair have not been explored in UF tumorigenesis. In the Eker rat UF model, a germline mutation in the Tsc2 tumor suppressor gene predisposes to UFs, which arise due to "second hits" in the

SUBMITTER: Prusinski Fernung LE 

PROVIDER: S-EPMC6203880 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature