The Effects of Iodoacetic Acid on Oxidative Stress Markers in the Mouse Ovary.

The incorporation of water disinfectants into the main water supply has significantly decreased the incidence of waterborne diseases. However, the interaction between disinfectants and organic material generates water disinfection byproducts (DBPs) such as iodoacetic acid (IAA). IAA is an ovarian toxicant, but little is known about its mechanisms of toxicity. Thus, we tested the hypothesis that IAA exposure causes ovarian toxicity through oxidative stress pathways. Adult CD-1 mice were dosed with vehicle control (reverse osmosis water) or IAA (2.7-2695.7 μM) for 35 days. Then, whole ovaries or isolated antral follicles were collected for measurement of expression of several enzymes that regulate oxidative stress (Gpx1, Gpx2, Gsr, Gss, Gsta1, Gstm1, Gsto1, Gstp1, Gstt1, Sod1, Sod2, and Cat). In other experiments, antral follicles were cultured with vehicle control ± the antioxidant Trolox or IAA (2-15 μM) ± the antioxidant Trolox for 96 h and follicle growth was measured every 24 h. Media were collected for estradiol measurements. IAA decreased Cat, Sod1, Gss, Gsta1, Gstp1, and Gstt1 and increased Gstm1 expression in whole ovaries compared to control in vivo. IAA decreased Sod2 and Gpx2 and increased Gstp1 expression in antral follicles compared to control in vivo. IAA increased Gpx1 and Gsto1 expression in antral follicles compared to control in vitro. IAA inhibited follicle growth and reduced estradiol levels, whereas Trolox rescued follicles from IAA-induced inhibition of follicle growth and estrogen levels in vitro. Collectively, these data indicate that IAA exposure causes ovarian toxicity by altering oxidative stress pathways in the mouse ovary.