Moustafa Gihan G, Ahmed Amal A M
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Egypt.
Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez canal University, Egypt.
Toxicol Rep. 2016 Aug 28;3:685-695. doi: 10.1016/j.toxrep.2016.08.008. eCollection 2016.
Environmental xenoestrogen contaminant bisphenol A (BPA), widely used as a monomer in the manufacture of epoxy, polycarbonate plastics and polystyrene resins. However, exposure to BPA has raised concerns, and the negative impacts of its exposure on reproduction have been controversial. The purpose of this work was directed to assess the potential adverse effects of BPA on dam rats and their first generation females in a comparative toxicological study. Fifteen pregnant female rats were classified into three equal groups; first group was orally administered corn oil and served as control (group1), second and third groups were orally administered BPA at dose levels of 50 and 200 mg/kg b.wt respectively (groups 2 & 3). The administration was carried out daily from zero day through the gestation period (21 days) until the last day of the lactation period (21days) and was extended after weaning for three months, in which female off springs of first generation (F1) of the three groups of dams were classified into; F1control group (group 4), F1 group treated with low dose of BPA (group 5) and F1 group treated with high dose of BPA (group 6) which continued in daily oral administration of BPA at the same previously mentioned doses for three months. The results elucidated a clear marked DNA fragmentation in the ovary of both dam and F1 female groups especially at higher examined concentration. Also, the data demonstrated a significant increase in the serum levels of GGT, ALP, glucose, total cholesterol, triglycerides, LDH and also in the serum level of estrogen hormone. Meanwhile, our study recorded a significant decrease in total protein, catalase, GST, HDL and FSH hormone in both treated dam and F1 female groups which was more significantly decreased in F1 female rats. Moreover, our experiment illustrated up-regulation in the immunoexpression of ERβ in ovary, uterus and liver of dam and F1 female groups. The histopathological investigation showed degeneration in the epithelial lining of ovarian follicles, submucosal leukocytic infiltration and increase in vaculation of hepatic cells with proliferation of kupffer cells. The lesions were more sever in groups 3 & 6 of both dam and their F1 females. Our data speculated that long- term exposure to BPA at 50 and 200 mg/kg.b.wt. depicted total genomic damage, significant alterations in liver enzymes, lipid profile, antioxidant enzymes and reproductive hormones with up-regulation in the expression of ERβ which were more significantly perturbed in group 3 and group 6 of both dam and F1 female rats.
环境异雌激素污染物双酚A（BPA），被广泛用作制造环氧树脂、聚碳酸酯塑料和聚苯乙烯树脂的单体。然而，接触双酚A引发了人们的担忧，其接触对生殖的负面影响一直存在争议。这项工作的目的是在一项比较毒理学研究中评估双酚A对母鼠及其第一代雌性后代的潜在不利影响。将15只怀孕的雌性大鼠分为三组，每组数量相等；第一组口服玉米油作为对照（第1组），第二组和第三组分别以50和200毫克/千克体重的剂量口服双酚A（第2组和第3组）。给药从第0天开始，持续整个妊娠期（21天）直至哺乳期最后一天（21天），并在断奶后延长三个月，在此期间，三组母鼠的第一代雌性后代（F1）分为：F1对照组（第4组）、低剂量双酚A处理的F1组（第5组）和高剂量双酚A处理的F1组（第6组），它们继续以相同的上述剂量每日口服双酚A三个月。结果表明，母鼠和F1雌性组的卵巢中均出现明显的DNA片段化，尤其是在较高检测浓度下。此外，数据显示γ-谷氨酰转移酶、碱性磷酸酶、葡萄糖、总胆固醇、甘油三酯、乳酸脱氢酶的血清水平以及雌激素的血清水平均显著升高。同时，我们的研究记录了在处理过的母鼠和F1雌性组中，总蛋白、过氧化氢酶、谷胱甘肽-S-转移酶、高密度脂蛋白和促卵泡激素水平均显著下降，在F1雌性大鼠中下降更为明显。此外，我们的实验表明，母鼠和F1雌性组的卵巢、子宫和肝脏中雌激素受体β（ERβ）的免疫表达上调。组织病理学研究显示，卵巢卵泡上皮衬里退化、黏膜下白细胞浸润以及肝细胞空泡化增加，枯否细胞增殖。在母鼠及其F1雌性的第3组和第6组中，病变更为严重。我们的数据推测，长期以50和200毫克/千克体重的剂量接触双酚A会导致全基因组损伤、肝酶、血脂谱、抗氧化酶和生殖激素的显著改变，同时ERβ表达上调，在母鼠和F#1雌性大鼠的第3组和第6组中受到的干扰更为明显。
