(282) Iodoacetic Acid Inhibits Ovarian Follicle Growth Through Oxidative Stress Pathways in Mice

Audrey Fields¹, and Jodi Flaws¹

1. Department of Comparative Biosciences and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL

Abstract Text:

The incorporation of water disinfectants into the main water supply has significantly decreased the presence of waterborne diseases such as cholera. However, the interaction between disinfectants and organic material generates water disinfection byproducts (DBPs). Iodoacetic acid (IAA) is an unregulated DBP that has been reported to be a reproductive toxicant. Our previous studies show that IAA causes ovarian toxicity, but the mechanisms underlying IAA-induced ovarian toxicity were unknown. Thus, we tested the hypothesis that IAA exposure inhibits follicular growth through a mechanism involving oxidative stress pathways. In addition, we tested whether the introduction of an antioxidant to IAA-exposed follicles would rescue follicular growth. To test these hypotheses, ovarian antral follicles were collected from CD-1 mice between 40 and 42 days of age. The follicles were either incubated in supplemented media containing vehicle control (water), IAA (2µM, 5µM, 10µM, 15µM), Trolox (5µM), or IAA (10µM) + Trolox (5µM) for 96 hours. At 0 hour, 24 hours, 48 hours, 72 hours, and 96 hours, follicle growth was measured over the 96-hour period. Following the 96-hour incubation, follicles were collected, and then RNA was extracted, reverse transcribed, and subjected to quantitative polymerase chain reaction (qPCR) to analyze the expression of regulators of oxidative stress, including glutathione markers (Gpx1, Gpx2, Gsr, Gss, Gsta1, Gstm1, Gsto1, Gstp1 Gstt1), superoxide dismutase markers (Sod1, Sod2), and catalase. IAA exposure (10µM) significantly decreased follicular growth at 96 hours when compared to control.  Further, IAA exposure significantly increased expression of Gpx1 and Gsto1 when compared to control.  However, IAA exposure did not alter Gpx2, Gsr, Gsta1, Gstm1, Gstp1, Gstt1, Sod1, Sod2, or Cat expression compared to control. Exposure to Trolox (5µM) alone or IAA (10µM) + Trolox (5µM) resulted in follicles growing in a similar manner to controls. Collectively, these data indicate that IAA exposure inhibits follicle growth through oxidative stress pathways in vitro. Supported by NIH R21 ES028963.