Monohaloacetic acid drinking water disinfection by-products inhibit follicle growth and steroidogenesis in mouse ovarian antral follicles in vitro

Abstract

Water disinfection greatly reduced the incidence of waterborne diseases, but the reaction between disinfectants and natural organic matter in water leads to the formation of drinking water disinfection by-products (DBPs). DBPs have been shown to be toxic, but their effects on the ovary are not well defined. This study tested the hypothesis that monohalogenated DBPs (chloroacetic acid, CAA; bromoacetic acid, BAA; iodoacetic acid, IAA) inhibit antral follicle growth and steroidogenesis in mouse ovarian follicles. Antral follicles were isolated and cultured with either vehicle or DBPs (0.25–1.00 mM of CAA; 2–15 µM of BAA or IAA) for 48 and 96 h. Follicle growth was measured every 24 h and the media were analyzed for estradiol levels at 96 h. Exposure to DBPs significantly inhibited antral follicle growth and reduced estradiol levels compared to controls. These data demonstrate that DBP exposure caused ovarian toxicity in vitro.

Endocrine Disruptors in Water and Their Effects on the Reproductive System

“…In adult rabbits, dibromoacetic acid decreased the number of primordial follicles compared to the non-exposed rabbits [48]. In mice, iodoacetic acid inhibited antral follicle growth and reduced estradiol production by ovarian follicles in vitro [49]. To determine the mechanisms by which iodoacetic acid caused these alterations, Gonsioroski et al [50] analyzed the gene expression and sex steroid hormone levels of mouse ovarian follicles in vitro.…”

Iodoacetic acid inhibits follicle growth and alters expression of genes that regulate apoptosis, the cell cycle, estrogen receptors, and ovarian steroidogenesis in mouse ovarian follicles

“…IAA has also been shown to be an ovarian toxicant. Our laboratory established that IAA inhibited antral follicle growth and reduced estradiol production by mouse ovarian follicles in vitro [19], however, the mechanisms by which IAA inhibits ovarian follicle growth and reduces estradiol levels were not determined. In addition, it is estimated that adult women absorb 3.42 mg/day of DBPs and about 3 μg/L/h reach the ovaries, which equates to approximately 0.09 μg/ml/day reaching the ovary [20], raising concern that the ovary is a target tissue for DBP-induced toxicity.…”

Exposure Characterization of Haloacetic Acids in Humans for Exposure and Risk Assessment Applications: An Exploratory Study

“…Chlorinated HAAs (e.g., DCAA and TCAA acid) induce oxidative stress in rats by reducing glutathione (GSH) synthesis [17]. Monohaloacetic acids (including chloro-, bromo-, and iodoacetic acid) can cause genomic DNA damage in Chinese hamster ovary cells, and inhibit follicle growth and steroidogenesis in mice ovary [13,18,19,20].…”

“…Currently, no study has evaluated whether urinary MCAA can be used as a reliable exposure biomarker. This is important because MCAA is more cytotoxic and genotoxic than DCAA and TCAA [19,20,44]. Therefore, an exploratory human biomonitoring study was designed, and participants were recruited from two water systems to determine HAA composition in urine and the corresponding drinking water, compare inter- and intra-individual exposure variability, and investigate potential correlations across urinary biomarkers and between urinary and drinking measures.…”