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目的研究孕期双酚A(BPA)暴露对子代雌性大鼠卵巢类固醇激素合成的影响。方法选择SPF级3月龄的健康成年SD大鼠,按雌雄比为2∶1同笼配种。取妊娠大鼠20只,随机分成4组,于妊娠第5天~第20天,分别按0,10,50,250mg/(kg·d)BPA进行灌胃染毒。母鼠正常分娩,观察雌性仔鼠生长发育变化至10周龄,确定发情间期后处死动物。ELISA法测定血清中卵泡刺激素(FSH)、黄体生成素(LH)、孕酮(P4)、雌二醇(E2)及睾酮(T)水平;实时PCR测定卵巢中类固醇激素急性调节蛋白(StAR)、胆固醇侧链裂解酶(P450scc)、3β羟类固醇脱氢酶(3β-HSD)、细胞色素P450-17α羟化酶(P450-17α)、17β-羟类固醇脱氢酶(17β-HSD)、芳香化酶(P450arom)mRNA的基因表达。结果出生28~36d期间,50和250mg/kg组体质量与对照组比较明显增加,差异有统计学意义(P<0.05);各剂量组与对照组相比,T水平明显下降,差异有统计学意义(P<0.05);50和250mg/kg组与对照组相比,LH、FSH、E2水平明显减少,差异有统计学意义(P<0.05));各剂量组卵巢中17β-HSD mRNA的基因表达与对照组比较明显降低,差异有统计学意义(P<0.05);50和250mg/kg组P450arom mRNA的基因表达与对照组比较明显降低(P<0.05),差异有统计学意义。结论孕期暴露BPA对子代雌性大鼠卵巢中类固醇激素合成酶的基因表达有一定的影响,可能影响类固醇激素合成,进而影响下丘脑-垂体-卵巢轴的正常调节。
Objective To investigate the effects of BPA exposure during pregnancy on ovarian steroidogenesis in female offspring. Methods SPF 3-month-old healthy adult SD rats were selected and sowed at the same ratio of 2: 1. Twenty pregnant rats were randomly divided into four groups. The rats were orally administered with 0, 10, 50 and 250 mg / (kg · d) BPA on the 5th to 20th day of gestation respectively. Maternal normal childbirth, growth observed in female offspring changes to 10 weeks of age, to determine the estrus period after the animals were sacrificed. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P4), estradiol (E2) and testosterone (T) were measured by ELISA. The level of steroid hormone acute regulatory protein ), Cholesterol side chain lyase (P450scc), 3β hydroxysteroid dehydrogenase (3β-HSD), cytochrome P450-17α hydroxylase (P450-17α), 17β-hydroxysteroid dehydrogenase Aromatase (P450arom) mRNA Gene Expression. Results The body mass at 50 and 250 mg / kg at 28 ~ 36 d after birth was significantly increased compared with that in the control group (P <0.05). Compared with the control group, the T level was significantly decreased in all dosage groups, with statistical differences (P <0.05). Compared with control group, the levels of LH, FSH and E2 in 50 and 250 mg / kg groups were significantly decreased (P <0.05), and the levels of 17β-HSD mRNA (P <0.05). The gene expression of P450arom mRNA in 50 and 250 mg / kg group was significantly lower than that in control group (P <0.05), the difference was statistically significant. Conclusion Exposure to BPA during pregnancy may affect the gene expression of steroid hormone synthetase in the ovary of offspring female rats, which may affect steroid hormone synthesis and further affect the normal regulation of hypothalamic-pituitary-ovarian axis.