新生儿期不同剂量双酚A暴露对雌性大鼠青春发育的影响

Impact of neonatal exposure to different doses of bisphenol A on puberty in female rats

摘要:

目的 研究新生儿期不同剂量双酚A（BPA）暴露对雌性大鼠阴道开口时间（VOD）和下丘脑Kiss-1 基因、卵巢雌激素受体（ER）基因表达的影响。方法 将新生雌性Sprague-Dauley 大鼠随机分为6 组，即空白对照组、溶剂组、17β-雌二醇组（17β-estradiol，E₂，10 μg/d）、低剂量BPA 组（每日25 μg/kg）、中剂量BPA 组（每日50 μg/kg）和高剂量BPA 组（每日250 μg/kg），在生后0~6 d（PND 0~6）经皮下注射每日给药。记录VOD，并于当天处死，取出下丘脑、卵巢并称重，计算下丘脑、卵巢脏器系数。通过real-time PCR 的方法测定下丘脑Kiss-1 mRNA 和卵巢中ERα mRNA、ERβ mRNA 表达量。结果 与对照组相比，E₂ 组、中、高剂量BPA 组VOD 提前；E₂ 组下丘脑Kiss-1 mRNA、卵巢ERβ mRNA 表达量较对照组明显降低（P<0.05）。结论 新生儿期每日50 μg/kg 及250 μg/kg BPA 暴露可引起的大鼠青春期启动提前，但并非通过Kiss-1 基因表达改变来实现；新生儿期每日25 μg/kg BPA 暴露未引起大鼠青春期启动提前。

Abstract:

Objective To evaluate the effects of neonatal exposure to different doses of bisphenol A (BPA) on the vaginal opening day (VOD), hypothalamic Kiss-1 mRNA expression, and ovarian estrogen receptor (ER) mRNA expression in female rats. Methods Neonatal female Sprague-Dawley (SD) rats were randomly divided into six groups: blank control, vehicle, 17β-estradiol (17β-estradiol, E₂, 10 μg/d), low-dose BPA [25 μg(kg·d)], medium-dose BPA [50 μg(kg·d)], and high-dose BPA groups [250 μg(kg·d)]. The rats were subcutaneously injected with respective agents on postnatal days 0-6. The VOD was recorded, and each rat was sacrificed on the same day. The hypothalamus and ovary were taken and weighed, and the organ coefficients of hypothalamus and ovary were calculated. The hypothalamic Kiss-1 mRNA expression and ovarian ERα and ERβ mRNA expression were measured by real-time PCR. Results Compared with the control group, the E₂ and medium-and high-dose BPA groups had advanced VOD, and the E₂ group had significantly reduced hypothalamic Kiss-1 mRNA expression and ovarian ERβ mRNA expression (P<0.05). Conclusions Neonatal exposure to medium-and high-dose BPA[50 and 250 μg/(kg·d)] can induce precocious puberty in rats, but it may not result from the change in hypothalamic Kiss-1 mRNA expression. Neonatal exposure to low-dose BPA [25 μg/(kg·d)] does not induce precocious puberty in rats.