孕期染毒双酚A对雄性子代生殖发育影响

Effect of maternal exposure to bisphenol A during pregnancy on reproductive development in F1 male rats

目的探讨母鼠孕期接触双酚A对子代雄鼠生殖发育的影响及作用机制。方法将受孕SD雌鼠40只,随机分为双酚A0、10、50、250 mg/kg染毒组,以2 mL/kg容积自受孕第5 d灌胃染毒至第20 d;孕第21 d每组处理5只孕鼠,检测母鼠血中性激素水平,胎鼠数、死胎数、胎鼠重和胎盘重,高效液相色谱法检测母鼠血及胎盘中双酚A含量,另5只孕鼠自然分娩,待雄性子鼠性成熟后检测血中性激素水平,生殖器官脏器系数、病理、精子质量。结果 10、50 mg/kg剂量组母鼠血清中雌二醇(E2)含量分别为1 780.78、1 680.10 pmol/L,明显高于对照组的1361.74 pmol/L(P<0.01),低、中、高3个染毒组睾酮(T)含量分别为5.55、4.76、6.79 nmol/L,明显高于对照组的3.20 nmol/L(P<0.01);50、250 mg/kg剂量组雄性子鼠附睾及前列腺脏器系数分别为0.297、0.325和0.153、0.173,均高于对照组(P<0.01),镜下可见附睾间质及前列腺上皮有增生改变;250 mg/kg剂量组精子活动率为52.9%,明显低于对照组的67.4%(P<0.05)。结论孕期染毒双酚A对胎鼠发育无明显影响,但影响子鼠生殖器官发育和精子生成质量。

Objective To observe the growth and development of F1 male fetus and changes in reproductive organs of the rats after maternal exposure to bisphenol A（BPA） and to explore the effect of maternal exposure to BPA during pregnancy on the reproductive development in F1 male rats. Methods Forty pregnant Sprague-Dawley rats were randomed into 4 groups,including vehicle control（ corn oil）and BPA treatment groups （ 10,50, and 250 mg/kg, respectively） with the volume of 2 ml/kg. The rats were garaged once a day from the 5th day to the 20th day during pregnancy. Five rats in each group were anesthetized on the 21st day. Maternal sex hormone in serum,fetal number,dead fetus number,fetal weight, and placental weight were determined. BPA level in blood and placenta of the mother rats was detected with high performance liquid chro- matography （HPLC） method. Ther rats delivered naturally by the other 5 rats in each group were feeded untill sexual maturity. The concentration of sex hormone in serum of F1 male rats as well as organ coefficients of reproductive organ,histopathological changes, and sperm quality were measured. Results Estradiol （E2 ） level in serum of mother rats in 10 and 50 mg/kg dosage groups were 1 780. 78 and 1 680. 10 pmol/L, significantly higher than that of the control group （ 1 361.74 pmol/L） （P 〈0. 05）. The testosterone level in three treatment groups were 5.55,4. 76,and 6. 79 nmol/L and were significantly different compared with that of the control group（3.20nmol/L） （P 〈 0. 05 ）. The epididymis and prostate organ coefficients of the male offsprings of 50 and 250 mg/kg exposure groups were 0. 297,0. 325 and 0. 153,0. 173 ,higher than those of the control group （0. 253 and 0. 113） with significant differences（P 〈0. 05 for all）. There was hyperplasia change in epididymis interstitium and prostatic intraepithelia. The sperm motility rate of 250 mg/kg dose group was 52. 9% ,significantly lower than that of the control group（67. 4% ,P 〈 0. 05 ）. Conclusion The administration of BPA to female rats during pregnancy does not affect fetal development,but interferes with the development of reproductive organ and sperm quality of F1 male rats.