Endocrine-disrupting chemicals and uterine fibroids

Abstract

Uterine fibroids are the most frequent gynecologic tumor, affecting 70–80% of women over their lifetime. Although these tumors are benign, they can cause significant morbidity and may require invasive treatments such as myomectomy and hysterectomy. Many risk factors for these tumors have been identified, including environmental exposures to endocrine disrupting chemicals (EDCs), e.g. genestein, diethylstilbestrol etc. Uterine development may be a particularly sensitive window to environmental exposures, as some perinatal EDC exposures have been shown to increase tumorigenesis in both rodent models and human epidemiological studies. While the mechanisms by which EDC exposures may increase tumorigenesis are still being elucidated, epigenetic reprogramming of the developing uterus is an emerging hypothesis. Given the remarkably high incidence of uterine fibroids, and their significant impact on women’s health, understanding more about how prenatal exposures to EDCs (and other environmental agents) may increase fibroid risk could be key to developing prevention and treatment strategies in the future.

Exposure to endocrine disruptors during adulthood: consequences for female fertility

“…Multiple recent reviews have previously summarized the effects of developmental exposure to EDCs (Katz et al 2016; Walker and Gore 2016; Zama and Uzumcu 2010). Thus, this review focuses on adult exposure to synthetic EDCs such as pesticides (organochlorines, organophosphates, carbamates, pyrethroids, and triazines), heavy metals (arsenic, lead, and mercury), diethylstilbesterol, plasticizer alternatives (di-(2-ethylhexyl) phthalate and bisphenol A alternatives), 2,3,7,8-tetrachlorodibenzo-p-dioxin, nonylphenol, polychlorinated bisphenyls, triclosan, and parabens (Figures 1 and 2, Table 1).…”

Developmental Environmental Exposure Alters the Epigenetic Features of Myometrial Stem Cells

“…15 The epigenomic programming that occurs during development exhibits a high degree of plasticity, and is modifiable by extrinsic factors such as environmental exposures. 16,17 …”

“…However, environmental health studies are lacking on stem cells. 17 UF growth and progression depend on a specialized subpopulation of tumor cells, termed tumor initiating cells (TICs). 3,23 Thus, TICs represent a critical therapeutic target, but the molecular mechanisms that regulate them are poorly understood.…”

“…17,26 Early life exposure to EDC compounds have been connected to increased risk of adult onset of UFs in women. 27,28 Minority communities are particularly at risk for hazardous environmental exposures.…”

'Estrogens' in the Context of Endometrial Neoplasia

“…Uterine fibroids are the most frequent gynecologic tumor, affecting 70% to 80% of women over their lifetime [33]. Jeong et al, in order to investigate the number of leiomyoma patients-exposed to BPA and to observe whether the serum concentration of BPA is related to leiomyoma growth, divided leiomyoma patients into three groups; the mean BPA concentrations were 0.274 ± 0.063 ng/mL in the mild group, 0.346 ± 0.064 ng/mL in the moderate and 0.647 ± 0.039 ng/mL in the severe group [34].…”