Department of Reproductive medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
Hum Exp Toxicol. 2020 Jul;39(7):890-905. doi: 10.1177/0960327120903489. Epub 2020 Feb 7.
2,3,7,8-Tetrachlorodibenzo--dioxin (TCDD) is a ubiquitous environmental contaminant in the environment. The developmental period is more sensitive to TCDD and there is a possibility that maternal exposure to TCDD may affect in adulthood. Adult female Wistar rats were exposed to 0.5, 1.0, and 2.0 µg/kg TCDD during the critical stage of organogenesis, that is, on GD15. The results revealed a significant decrease in indices of reproductive organ weight in adult male rats exposed to prenatal TCDD, and dose-dependent reduction in epididymal sperm reserves, percent motile, and viable sperm with an increase in percent morphological abnormal sperm. Polymerase chain reaction analysis revealed downregulated expression levels of steroidogenic markers such as steroidogenic acute regulatory, cholesterol side-chain cleavage, and 3β- and 17β-hydroxysteroid dehydrogenase (HSDs) in experimental rats. Immunofluorescence sections portrayed reduced distribution of 3β- and 17β-HSD proteins in testes of experimental rats. Furthermore, spermatogenic markers (acid phosphatase, alkaline phosphatase, lactate dehydrogenase, and sorbitol dehydrogenase) were significantly altered in the testes. Serum levels of testosterone, follicle stimulating hormones, and luteinizing hormone were significantly decreased. Testicular levels of hydrogen peroxide and lipid peroxidation were significantly elevated with a decline in superoxide dismutase, catalase, glutathione peroxidase activities, and total thiol levels. Moreover, histological and morphometric examination of testicular cross-sections depicted degenerative changes. Male fertility assessment in adult rats revealed a significant decrease in mating index, fertility index, and mean number of pre- and postimplantations with an increase in pre- and postimplantation losses in rats cohabited with in utero TCDD-exposed adult males. In conclusion, the findings of this study provided clear evidence that maternal exposure to TCDD during the critical stage of development results in suppressed reproductive health in adulthood.
2,3,7,8-四氯二苯并对二恶英(TCDD)是环境中普遍存在的环境污染物。发育期对 TCDD 更为敏感,母体接触 TCDD 有可能影响成年后的健康。成年雌性 Wistar 大鼠在器官发生的关键阶段(即 GD15 时)暴露于 0.5、1.0 和 2.0μg/kg TCDD 中。结果显示,产前 TCDD 暴露的成年雄性大鼠生殖器官重量指数显著降低,附睾精子储备量、精子活力和可存活精子比例呈剂量依赖性降低,畸形精子比例增加。聚合酶链反应分析显示,实验大鼠中类固醇生成标志物如类固醇急性调节蛋白、胆固醇侧链裂解酶和 3β-和 17β-羟甾脱氢酶(HSDs)的表达水平下调。免疫荧光切片显示,实验大鼠睾丸中 3β-和 17β-HSD 蛋白的分布减少。此外,睾丸中的精子发生标志物(酸性磷酸酶、碱性磷酸酶、乳酸脱氢酶和山梨醇脱氢酶)发生显著改变。血清中睾酮、促卵泡激素和黄体生成素水平显著降低。睾丸中过氧化氢和脂质过氧化水平显著升高,超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性和总巯基水平降低。此外,睾丸横切片的组织学和形态计量学检查显示出退行性变化。成年大鼠的雄性生育能力评估显示,交配指数、生育指数和着床前和着床后的平均数量显著降低,与宫内 TCDD 暴露的成年雄性大鼠同居的大鼠的着床前和着床后损失增加。总之,本研究的结果提供了明确的证据,表明母体在发育的关键阶段接触 TCDD 会导致成年后生殖健康受损。