College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, China.
Food Chem Toxicol. 2018 Jun;116(Pt B):11-19. doi: 10.1016/j.fct.2018.04.011. Epub 2018 Apr 5.
The present study investigated the reproductive and developmental toxicity of male offspring induced by prenatal ZEN exposure and explored the possible mechanism. 64 pregnant rats were allocated into four groups and fed with ZEN contaminated (0, 5, 10 and 20 mg/kg) diet during the whole gestation period. The results showed that, F1 male foetal viability was not affected while newborn bodyweight (BW) was significantly decreased after prenatal exposure to ZEN. Decreased BW was found on postnatal day (PND) 21 but not on PND 63 in ZEN exposed male rats. Moreover, adult testis weight increased with seminiferous tubules atrophy as well as decreased spermatocytes and mature sperms (35% and 31%) in ZEN-treated rats. Meanwhile, circulating levels of luteinizing hormone and testosterone decreased while estradiol increased in ZEN-treated rats. These impairments concurred with down-regulations of 3β-HSD and StAR in both mRNA and protein levels in weaned and adult testis. Furthermore, gene and protein expressions of GnRHr and Esr1 were inhibited in the ZEN-treated foetal brain. These results suggested that prenatal ZEN exposure disrupted the system regulating the reproductive hormones and testis development through hormone related genes, which may result in a reproductive dysfunction in adult male offspring.
本研究探讨了孕期 ZEN 暴露对雄性后代生殖发育毒性及其可能机制。64 只孕鼠在整个孕期给予 ZEN 污染(0、5、10 和 20mg/kg)饮食,并分为四组。结果表明,F1 雄性胎仔存活率不受影响,但新生仔鼠体重(BW)在孕期 ZEN 暴露后显著降低。在 ZEN 暴露雄性仔鼠中,BW 在出生后第 21 天(PND21)下降,但在 PND63 时未下降。此外,成年睾丸重量增加,曲细精管萎缩,精母细胞和成熟精子减少(35%和 31%)。同时,ZEN 处理大鼠的循环黄体生成素和睾酮水平降低,雌二醇水平升高。这些损伤与断奶和成年睾丸中 3β-HSD 和 StAR 的 mRNA 和蛋白水平下调一致。此外,ZEN 处理胎鼠大脑中的 GnRHr 和 Esr1 的基因和蛋白表达受到抑制。这些结果表明,孕期 ZEN 暴露通过激素相关基因破坏了生殖激素和睾丸发育的调节系统,可能导致成年雄性后代生殖功能障碍。