邻苯二甲酸（2-乙基己基）酯孕期暴露对雌性子代大鼠性发育的影响

Effects of in utero exposure to di （2-ethylhexyi） phthalate on sexual development in female offspring

目的观察邻苯二甲酸（2-乙基己基）酯（DEHP）对雌性子鼠性发育的影响。方法妊娠12d（GD12）Wistar孕鼠，称重编号，用随机数字表法分为玉米油对照组和1、250、750、1000mg·kg^-1·d^-1DEHP染毒组，每组10只，GD12～17灌胃染毒。观察雌性子代大鼠出生后第14～17天（PND14～17）眼睛完全睁开时间；PND22处死计算脏器系数；PND30～38观察阴道完全开口时间（若PND30—38阴道未开口则持续观察至成年期），称量当日体重，并记录首次排卵时间。结果对照组和1、250、750、1000mg·kg^-1·d^-1DEHP染毒组子鼠眼睛完全睁开时间分别为（15．8±0．4）d、（16．3±0．6）d、（16．0±0．6）d、（15．9±0．6）d、（15．8±0．4）d，各组间比较差异无统计学意义（F=1．363，P=0．262）。750及1000mg·kg^-1·d^-1剂量组部分子鼠阴道永久未开口，未开口百分率分别为62．50％（15／24）、81．25％（26／32），与对照组比较，差异有统计学意义（X2值分别为84．92、132．79，P值均〈0．01）。对照组和1、250、750、1000mg·kg^-1·d^-1DEHP染毒组雌性子鼠阴道开口时间分别为（32．7±1．3）d、（33．3±1．5）d、（32．2±1．5）d、（33．1±1．3）d、（33．3±1．2）d；阴道开口时体重分别为（91．56±6．65）g、（93．79±6．28）g、（92．98±8．48）g、（100．57±6．47）g、（103．83±8．24）g。协方差分析显示，修正体重后阴道开口时间各组间比较，差异有统计学意义（F=3．075，P〈0．05），其中250mg·kg^-1·d^-1。组比对照组提前（t=-2．056，P〈0．05）；体重对阴道开口的影响有统计学意义（F=40．857，P〈0．05）。结论GD12～17DEHP染毒可影响雌性子代大鼠阴道开口，引发阴道闭锁畸形，导致其性发育异常。

Objective To evaluate the ability of di（2-ethylhexyl）phthalate （DEHP） with inducing damage in sexual development of female offspring rats after maternal exposure. Methods On gestational day （GD） 12, pregnant Wistar rats were weighed, encoded and randomly assigned to 5 groups （10 dams per group）. From GD 12 through GD 17 each dam was dosed daily by garage with either corn oil （ vehicle control, 1mg·kg^-1·d^-1 ） or DEHP （1, 250, 750 and 1000 mg·kg^-1·d^-1 ）. Then female offspring were monitored for eye opening on postnatal day （PND） 14 -17, organ coefficient on PND 22 and the time to vaginal opening on PND 30 - 38 （ if vagina did not open during the period, observation time should extent to adult）, as well as body weight, time to first estrus. Results No significant changes were observed on eye opening at any dose, which were （15.8±0.4） d, （16.3 ±0.6） d, （16.0±0.6） d, （15.9±0.6） d, （15.8 ±0. 4） d respectively in control, 1, 250, 750 and 1000 mg·kg^-1·d^-1 （F= 1. 363, P =0. 262）. However, 62. 50% （15/24） , 81.25% （26/32）female offspring were permanently absence of vaginal orifice in 750 and 1000 mg·kg^-1·d^-1 groups respectively, while control, 1 and 250 mg·kg^-1·d^-1 groups developed normally with vaginal orifices （ χ2 values were 84. 92, 132. 79, respectively, P 〈0. 01 ）. The ages ofvaginal opening were （32.7±1.3） d, （33.3±1.5） d, （32.2±1.5） d, （33.1 ±1.3） d, （33.3±1.2） d and the body weight were （91.56 ±6. 65） g, （93.79 ±6.28） g, （92.98 ±8.48） g, （100.57 ± 6.47） g, （103.83 ±8.24） g in control, 1, 250, 750 and 1000mg·kg^-1·d^-1＇.Mter covariance adjustment for body weight, which can statistically influenced the age of vaginal opening （ F = 40. 857, P 〈 0.05）, difference were found at the age of vaginal opening （F= 3. 075, P〈 0.05 ） , and 250mg·kg^-1·d^-1 group was advanced than control （ t = - 2. 056, P 〈 0. 05 ）. Conclusion Exposure to DEHP in utero from GD 12 - 17 can result in abnormalities of sexual development such as the time to vaginal opening and vaginal atresia.