Multigenerational Effects of an Environmentally Relevant Phthalate Mixture on Reproductive Parameters and Ovarian miRNA Expression in Female Rats.
Multigenerational Effects of an Environmentally Relevant Phthalate Mixture on Reproductive Parameters and Ovarian miRNA Expression in Female Rats.
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环境相关邻苯二甲酸盐混合物对雌性大鼠生殖参数和卵巢 miRNA 表达的多代影响。
DOI：
10.1093/toxsci/kfac066
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Flaws,JodiA
中科院分区：
文献类型：
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作者：
Gonsioroski,AndressaV;Aquino,ArianaM;Alonso-Costa,LuizG;Barbisan,LuisF;Scarano,WellersonR;Flaws,JodiA
邻苯二甲酸酯是许多消费品中使用的内分泌干扰化学品。我们的实验室以前开发了一种与环境相关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混合物是否会影响F1和F2代雌性大鼠的生殖参数和卵巢后转录。因此，我们检验了母体暴露于邻苯二甲酸酯混合物影响F1和F2代雌性大鼠卵泡生成、类固醇生成和卵巢microRNA（miRNA）的假设。将妊娠雌性大鼠分为4组，从妊娠第10天至产后第21天每天经口给予玉米油（对照组）、20 μg/kg/天、200 μg/kg/天或200 mg/kg/天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代雌性大鼠的卵泡生成，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改变了雌性大鼠F1和F2代中与细胞周期和类固醇生成相关的一些基因的卵巢表达。该混合物还增加了卵巢中与卵母细胞成熟过程有关的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代雌性大鼠的卵泡生成和类固醇生成，并改变F1代雌性大鼠卵巢miRNA的表达。
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.