Department of Comparative Biosciences, University of Illinois, Urbana, 61802, IL, USA.
Department of Crop Sciences and the Safe Global Water Institute, University of Illinois, Urbana, 61802, IL, USA.
Biol Reprod. 2021 Oct 11;105(4):1030-1042. doi: 10.1093/biolre/ioab108.
Iodoacetic acid (IAA) is a water disinfection byproduct that is an ovarian toxicant in vitro. However, information on the effects of IAA on ovarian function in vivo was limited. Thus, we determined whether IAA exposure affects estrous cyclicity, steroidogenesis, and ovarian gene expression in mice. Adult CD-1 mice were dosed with water or IAA (0.5-500 mg/L) in the drinking water for 35-40 days during which estrous cyclicity was monitored for 14 days. Ovaries were analyzed for expression of apoptotic factors, cell cycle regulators, steroidogenic factors, estrogen receptors, oxidative stress markers, and a proliferation marker. Sera were collected to measure pregnenolone, androstenedione, testosterone, estradiol, inhibin B, and follicle-stimulating hormone (FSH) levels. IAA exposure decreased the time that the mice spent in proestrus compared to control. IAA exposure decreased expression of the proapoptotic factor Bok and the cell cycle regulator Ccnd2 compared to control. IAA exposure increased expression of the proapoptotic factors Bax and Aimf1, the antiapoptotic factor Bcl2l10, the cell cycle regulators Ccna2, Ccnb1, Ccne1, and Cdk4, and estrogen receptor Esr1 compared to control. IAA exposure decreased expression of Sod1 and increased expression of Cat, Gpx and Nrf2. IAA exposure did not affect expression of Star, Cyp11a1, Cyp17a1, Hsd17b1, Hsd3b1, Esr2, or Ki67 compared to control. IAA exposure decreased estradiol levels, but did not alter other hormone levels compared to control. In conclusion, IAA exposure alters estrous cyclicity, ovarian gene expression, and estradiol levels in mice.
碘乙酸(IAA)是一种水消毒副产物,在体外是一种卵巢毒物。然而,关于 IAA 对体内卵巢功能的影响的信息有限。因此,我们确定了 IAA 暴露是否会影响小鼠的动情周期、类固醇生成和卵巢基因表达。成年 CD-1 小鼠在饮用水中接受水或 IAA(0.5-500mg/L)处理 35-40 天,在此期间监测动情周期 14 天。分析卵巢中凋亡因子、细胞周期调节剂、类固醇生成因子、雌激素受体、氧化应激标志物和增殖标志物的表达。收集血清以测量孕烯醇酮、雄烯二酮、睾酮、雌二醇、抑制素 B 和卵泡刺激素(FSH)水平。与对照组相比,IAA 暴露减少了小鼠处于动情前期的时间。与对照组相比,IAA 暴露降低了促凋亡因子 Bok 和细胞周期调节剂 Ccnd2 的表达。与对照组相比,IAA 暴露增加了促凋亡因子 Bax 和 Aimf1、抗凋亡因子 Bcl2l10、细胞周期调节剂 Ccna2、Ccnb1、Ccne1 和 Cdk4 以及雌激素受体 Esr1 的表达。IAA 暴露降低了 Sod1 的表达,增加了 Cat、Gpx 和 Nrf2 的表达。与对照组相比,IAA 暴露对 Star、Cyp11a1、Cyp17a1、Hsd17b1、Hsd3b1、Esr2 或 Ki67 的表达没有影响。与对照组相比,IAA 暴露降低了雌二醇水平,但没有改变其他激素水平。总之,IAA 暴露改变了动情周期、卵巢基因表达和雌二醇水平在小鼠中。