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

Abstract

The reactions between disinfectants and organic matter or inorganic matter in source water generates disinfection by-products (DBPs) such as iodoacetic acid (IAA). DBPs are associated with health effects such as bladder cancer and adverse reproductive outcomes, but the effects of IAA on the ovary are not well known. This study determined whether IAA exposure affects ovarian follicle growth, steroidogenesis, and expression of apoptotic factors, cell cycle regulators, estrogen receptors, and steroidogenic factors in vitro. IAA exposure significantly decreased follicle growth, expression of cell cycle stimulators, and the proliferation marker Ki67. In contrast, IAA increased expression of the cell cycle inhibitor Cdkn1a. Moreover, IAA exposure increased expression of pro-apoptotic factors, whereas it decreased expression of anti-apoptotic factors. IAA exposure also altered expression of steroidogenic factors and estrogen receptors, disrupting steroidogenesis. These data demonstrate that IAA exposure inhibits follicle growth, decreases cell proliferation, and alters steroidogenesis in mouse ovarian follicles in vitro.

Androgenic and Teratogenic Effects of Iodoacetic Acid Drinking Water Disinfection Byproduct in Vitro and in Vivo

“…However, Kim et al found that IAA could inhibit the estrogenic activity of yeast cells . IAA also could inhibit the proliferation of mouse follicular cells in vitro and decrease sex steroid hormone levels by downregulating expression of Cyp17a1 , Hsd17b1 , and Cyp19a1 in steroidogenesis. , The discrepancies between our results and earlier studies may be associated with use of different end points, species of cells and animals, and in vivo and in vitro models.…”

“…Previous quantitative structure–activity relationship (QSAR) analyses have predicted that IAA may have developmental toxicity, which could lead to developmental malformation of the neural tube in mice . IAA could inhibit the proliferation of mouse ovarian follicular cells in vitro and decrease the levels of estradiol, testosterone, and androstenedione by disrupting steroidogenesis. , IAA could also inhibit the estrogenic activity of yeast cells . Our previous results of the in vivo and in vitro experiments have shown that IAA has thyroid disrupting effects and decreases the ovary weight of rats .…”

“…14 IAA could inhibit the proliferation of mouse ovarian follicular cells in vitro and decrease the levels of estradiol, testosterone, and androstenedione by disrupting steroidogenesis. 15,16 IAA could also inhibit the estrogenic activity of yeast cells. 17 thyroid disrupting effects and decreases the ovary weight of rats.…”

Endocrine Disruptors in Water and Their Effects on the Reproductive System

“…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. They showed that iodoacetic acid dysregulated the expression of apoptotic factors, cell cycle regulators, steroidogenic factors, and estrogen receptors, subsequently disrupting cell proliferation and steroidogenesis [50].…”

“…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. They showed that iodoacetic acid dysregulated the expression of apoptotic factors, cell cycle regulators, steroidogenic factors, and estrogen receptors, subsequently disrupting cell proliferation and steroidogenesis [50]. Narotsky et al assessed the combined toxicity of regulated DBPs (TTHMs, HAAs, or TTHMs and HAAs) on the fertility indices of rats [51].…”