Dept of Morphology, Federal University of Espírito Santo, Brazil.
Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil; Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
Toxicol Lett. 2018 Oct 1;295:99-114. doi: 10.1016/j.toxlet.2018.06.1068. Epub 2018 Jun 15.
Tributyltin chloride (TBT) is an obesogen associated with various metabolic and reproductive dysfunctions after in utero exposure. However, few studies have evaluated TBT's obesogenic effect on adult ovaries. In this study, we assessed whether TBT's obesogenic effects resulted in adult ovarian adipogenesis and other reproductive abnormalities. TBT was administered to adult female Wistar rats, and their reproductive tract morphophysiology was assessed. We further assessed the ovarian mRNA/protein expression of genes that regulate adipogenesis. Rats exposed to TBT displayed abnormal estrous cyclicity, ovarian sex hormone levels, ovarian follicular development and ovarian steroidogenic enzyme regulation. Rats exposed to TBT also demonstrated abnormal ovarian adipogenesis with increased cholesterol levels, lipid accumulation, and PPARγ, C/EBP-β and Lipin-1 expression. A negative correlation between the ovarian PPARγ expression and aromatase expression was observed in the TBT rats. Furthermore, TBT exposure resulted in reproductive tract atrophy, inflammation, oxidative stress and fibrosis. Ovarian dysfunctions also co-occurred with the uterine irregularities. Abnormal ovarian adipogenic markers occurring after TBT exposure may be associated with uterine irregularities. A positive correlation between the ovarian cholesterol levels and uterine inflammation was observed in the TBT rats. These findings suggest that TBT leads to ovarian obesogenic effects directly by abnormal adipogenesis and/or indirectly through adult reproductive tract irregularities.
三丁基锡氯化物 (TBT) 是一种与宫内暴露后各种代谢和生殖功能障碍有关的致肥胖物。然而，很少有研究评估 TBT 对成年卵巢的致肥胖作用。在这项研究中，我们评估了 TBT 的致肥胖作用是否导致成年卵巢脂肪生成和其他生殖异常。TBT 被给予成年雌性 Wistar 大鼠，并评估其生殖道形态生理学。我们进一步评估了调节脂肪生成的卵巢基因的 mRNA/蛋白质表达。暴露于 TBT 的大鼠表现出异常的动情周期性、卵巢性激素水平、卵巢卵泡发育和卵巢甾体生成酶调节。暴露于 TBT 的大鼠还表现出异常的卵巢脂肪生成，胆固醇水平升高、脂质积累以及 PPARγ、C/EBP-β 和 Lipin-1 表达增加。在 TBT 大鼠中观察到卵巢 PPARγ 表达与芳香酶表达之间存在负相关。此外，TBT 暴露导致生殖道萎缩、炎症、氧化应激和纤维化。生殖系统异常也与子宫不规则同时发生。TBT 暴露后出现的异常卵巢脂肪生成标志物可能与子宫不规则有关。在 TBT 大鼠中观察到卵巢胆固醇水平与子宫炎症之间存在正相关。这些发现表明，TBT 通过异常脂肪生成直接导致卵巢致肥胖作用，或者通过成年生殖道异常间接导致。
