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目的研究哺乳期母鼠暴露于双酚A(BPA)是否通过线粒体途径引起雄性仔鼠成年后睾丸的氧化损伤和凋亡。方法母鼠分娩后随机分为BPA高、中、低剂量组(50、5、0.01 mg/kg)和溶剂对照组。哺乳期内每天灌胃给药,仔鼠成年后取睾丸测定线粒体中丙二醛(MDA),琥珀酸脱氢酶(SDH),谷胱甘肽-过氧化物酶(GSHPX)和超氧化物歧化酶(SOD)的含量变化。Western blot检测睾丸内细胞色素c(Cyt C)及凋亡相关因子半胱氨酸天冬氨酸蛋白酶-3(caspase 3)和凋亡诱导因子(AIF)的表达。透射电镜观察睾丸细胞线粒体结构变化。结果 BPA组睾丸线粒体中MDA含量显著升高(P<0.05),SDH活性显著降低(P<0.05),中高剂量组SOD和GSHPx活性显著降低(P<0.05),Western blot结果显示Cyt C、caspase 3和AIF表达量均显著升高(P<0.05)。透射电镜观察中高剂量组各级生精细胞内出现线粒体肿胀,线粒体嵴模糊或消失。结论哺乳期接触一定剂量BPA可能通过线粒体途径诱导睾丸生精细胞的氧化损伤和凋亡,从而影响子代睾丸的发育。
Objective To investigate whether exposure of BPA to lactation induced oxidative damage and apoptosis of testis in male offspring through mitochondrial pathway. Methods The female rats were randomly divided into BPA high, medium and low dose groups (50, 5, 0.01 mg / kg) and solvent control group. Mice were given intragastric administration during lactation. Testis was used to determine mitochondrial MDA, SDH, GSHPX and superoxide Dismutase (SOD) content changes. Western blot was used to detect the expression of cytochrome c (Cyt C) and apoptosis related factors caspase 3 and AIF in testis. Transmission electron microscope observation of testicular cell mitochondrial structure changes. Results The contents of MDA in testis mitochondria of BPA group were significantly increased (P <0.05), the activity of SDH was significantly lower (P <0.05), and the activities of SOD and GSHPx in medium and high dose groups were significantly lower (P <0.05). Western blot results showed that Cyt C and caspase 3 and AIF were significantly increased (P <0.05). The mitochondria swollen and the mitochondrial cristae were blurred or disappeared in the medium and high dose groups. Conclusion Exposure to a dose of BPA during lactation may induce oxidative damage and apoptosis of spermatogenic cells in the testis through the mitochondrial pathway, thus affecting the development of testis in progeny.