胚胎期接触双酚A对雄鼠睾丸内PCNA和p53表达的影响

目的研究胚胎期接触双酚A(Bisphenol A,BPA)对雄性胎鼠睾丸发育的影响及睾丸内增殖细胞核抗原(Proliferating Cell Nuclear Antigen,PCNA)和p53表达的影响。方法母鼠怀孕后第2天对其灌服双酚A(剂量5,50,100 mg/ml/day),一直持续分娩,F1代雄性小鼠饲养至75日龄,观察BPA对仔鼠成年后睾丸结构和PCNA和p53表达的影响。结果发现BPA处理组睾丸发育受到抑制,曲细精管直径和管腔直径变小(P0.05),管腔内出现大量胞质残余体,部分管腔出现潴留管腔液,支持细胞生长受到抑制,生精细胞排列紊乱,细胞质出现空泡化。免疫组织化学结果显示在BPA处理组,PCNA除了在精原细胞大量表达外,在初级精母细胞中表达量明显升高(P0.05,P0.01),免疫荧光结果显示胚胎期接触BPA导致成年后睾丸内p53蛋白表达量显著升高(P0.05,P0.01)。结论胚胎期接触BPA对雄鼠睾丸发育有着长期的不良影响,可能源于BPA引起细胞的异常增殖和凋亡。

EFFECT OF EXPOSURE TO BISPHENOL A DURING EMBRYONIC PERIOD ON THE EXPRESSION OF PCNA AND P53 IN TESTES OF ADULT MALE OFFSPRINGS

Objective To evaluate the effects of Bisphenol A（BPA） administrated during the embryonic period on testes development and on the expression of proliferating cell nuclear antigen（PCNA） and p53 in testes.Methods BPA（at dose of 5,50,or 100 mg/kg/day） was given daily by gavage to dam mice during gestation.F1 male mice were bred until postnatal day 75.Results Morphological studies revealed that testis development was inhibited by BPA,the diameter of seminiferous tubule and luminal diameter being decreased significantly（P〈0.05）.There was redundant residual cytoplasm of regnaud and liquid retention in the lumen of seminiferous tubules.BPA-treated groups had germ cells in disordered arrangement,intraepithelial vacuoles were clearly observed,and at the same time sertoli cells were suppressed.Immunohistochemistry revealed that the expression of PCNA in spermatogonia and primary spermatocytes was increased in BPA-treated groups（P〈0.05,P〈0.01）.Immunofluorescence showed that the expression of p53 also increased in testes of adult males exposed to BPA during the embryonic period（P〈0.05,P〈0.01）.Conclusion BPA has long-term adverse effects on testis development after embryonic exposure,which may result from adnormal proliferation and apoptosis caused by BPA.