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目的探讨邻苯二甲酸二(2-乙基)己酯(DEHP)暴露对青春期前雌性大鼠性发育及生殖内分泌功能的影响及其可能机制。方法将40只健康3周龄雌性SD大鼠,随机分成对照组(玉米油)和3个实验组,每组10只。实验组按50、150、500mg/kg DEHP经口灌胃,连续染毒28天。观察阴道开口、乳房发育、第一次发情周期的日龄及体重,于末次染毒24小时后进行阴道涂片,确定动情间期,处死动物。Real-time PCR测定卵巢组织相关基因表达水平;ELISA法检测血清中卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P4)及睾酮(T)水平;通过病理学观察卵巢组织的变化;免疫组织化学法测定卵巢组织中PPARγ的表达。结果 500mg/kg组阴道开口日龄提前,150、500mg/kg组阴道开口时体重增加(P<0.05);150、500mg/kg组芳香化酶(P450Arom)mRNA表达与对照组比较,显著下降;各剂量组与对照组相比,T水平明显下降,150、500mg/kg组FSH、E2水平明显减少,而LH水平明显升高(P<0.05);150、500mg/kg组闭锁卵泡明显增多、黄体数目明显减少;150、500mg/kg组卵泡颗粒细胞和黄体颗粒细胞中PPARγ阳性光密度相对量明显高于对照组及50mg/kg组(P<0.05)。结论青春期前DEHP暴露对雌性大鼠性发育及生殖内分泌功能产生影响,其作用机制可能与激活PPARs有关。
Objective To investigate the effects of DEHP exposure on sexual development and reproductive and endocrine functions of pre-adolescent female rats and its possible mechanism. Methods Forty healthy three-week-old female Sprague-Dawley rats were randomly divided into control group (corn oil) and three experimental groups (n = 10). Experimental group by 50,150,500 mg / kg DEHP by oral gavage, continuous exposure to 28 days. Observe vaginal opening, breast development, the first estrous cycle of age and weight, in the last 24 hours after exposure to vaginal smear, to determine the estrus period, the animals were sacrificed. The levels of FSH, LH, E2, P4 and T were detected by Real-time PCR and Western blotting respectively. The changes of ovarian tissue were observed by pathology. The expression of PPARγ in ovarian tissue was detected by immunohistochemical method. Results The vaginal opening of 500mg / kg group was earlier than that of the control group (P <0.05). The mRNA expression of aromatase (P450Arom) in 150 and 500mg / kg group was significantly lower than that of the control group Compared with the control group, the levels of T decreased significantly in each dose group. The levels of FSH and E2 in 150 and 500 mg / kg groups decreased significantly and LH levels increased significantly (P <0.05) The number of corpus luteum significantly decreased. The relative optical density of PPARγ in 150,500 mg / kg group was significantly higher than that in control group and 50 mg / kg group (P <0.05). Conclusion Pre-puberty DEHP exposure has effects on sexual development and reproductive endocrine function in female rats, and its mechanism may be related to the activation of PPARs.