Department of Comparative Biosciences, University of Illinois Urbana-Champaign, Urbana, Illinois 61802, USA.
Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, SP 18618-689, Brazil.
Toxicol Sci. 2022 Aug 25;189(1):91-106. doi: 10.1093/toxsci/kfac066.
Phthalates are endocrine-disrupting chemicals used in many consumer products. Our laboratory previously developed an environmentally relevant phthalate mixture consisting of 6 phthalates and found that it disrupted female fertility in mice. However, it was unknown if maternal exposure to the mixture affects reproductive parameters and ovarian post-transcription in the F1 and F2 generation of female rats. Thus, we tested the hypothesis that maternal exposure to the phthalate mixture affects folliculogenesis, steroidogenesis, and ovarian microRNA (miRNA) in the F1 and F2 generations of female rats. Pregnant female rats were divided into 4 groups and orally dosed daily from gestational day 10 to postnatal day 21 with corn oil (control group), 20 μg/kg/day, 200 μg/kg/day, or 200 mg/kg/day of the phthalate mixture. Maternal exposure to the phthalate mixture impaired folliculogenesis in the F1 and F2 generations of female rats and affected steroidogenesis in the F1 generation of female rats compared to control. Further, the phthalate mixture altered ovarian expression of some genes related to the cell cycle and steroidogenesis compared to control in the F1 and F2 generations of female rats. The mixture also increased ovarian expression of rno-mir-184 that is involved with the oocyte maturation process. Collectively, our data show that maternal exposure to the phthalate mixture affects folliculogenesis and steroidogenesis in the F1 and F2 generations of female rats and alters ovarian miRNA expression in the F1 generation of female rats.
邻苯二甲酸酯是一种用于许多消费产品的内分泌干扰化学物质。我们实验室之前开发了一种具有环境相关性的邻苯二甲酸酯混合物，由 6 种邻苯二甲酸酯组成，发现它会破坏小鼠的雌性生育能力。然而，尚不清楚母体暴露于该混合物是否会影响雌性大鼠 F1 和 F2 代的生殖参数和卵巢转录后。因此，我们测试了以下假设：母体暴露于邻苯二甲酸酯混合物会影响 F1 和 F2 代雌性大鼠的卵泡发生、类固醇生成和卵巢 microRNA (miRNA)。将怀孕的雌性大鼠分为 4 组，从妊娠第 10 天到产后第 21 天，每天口服玉米油（对照组）、20μg/kg/天、200μg/kg/天或 200mg/kg/天的邻苯二甲酸酯混合物。与对照组相比，母体暴露于邻苯二甲酸酯混合物会损害 F1 和 F2 代雌性大鼠的卵泡发生，并影响 F1 代雌性大鼠的类固醇生成。此外，与对照组相比，邻苯二甲酸酯混合物还改变了 F1 和 F2 代雌性大鼠卵巢中与细胞周期和类固醇生成相关的一些基因的表达。该混合物还增加了卵巢中与卵母细胞成熟过程相关的 rno-mir-184 的表达。总的来说，我们的数据表明，母体暴露于邻苯二甲酸酯混合物会影响 F1 和 F2 代雌性大鼠的卵泡发生和类固醇生成，并改变 F1 代雌性大鼠的卵巢 miRNA 表达。
