Biomedical and Health Sciences Institute, Neuroscience Division, University of Georgia, Athens GA, USA.
Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, USA.
Chemosphere. 2021 Aug;276:130118. doi: 10.1016/j.chemosphere.2021.130118. Epub 2021 Feb 26.
The objective of this study was to evaluate the effects of gestational exposure to low doses of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) on pregnancy outcomes and offspring development. Pregnant Sprague-Dawley rats were orally dosed with vehicle, 5 μg/kg body weight (BW)/day of BPA, BPS and BPF, or 1 μg/kg BW/day of BPF on gestational days 6-21. Pregnancy and gestational outcomes, including number of abortions and stillbirths, were monitored. Male and female offspring were subjected to morphometry at birth, followed by pre- and post-weaning body weights, post-weaning food and water intakes, and adult organ weights. Ovarian follicular counts were also obtained from adult female offspring. We observed spontaneous abortions in over 80% of dams exposed to 5 μg/kg of BPF. BPA exposure increased Graafian follicles in female offspring, while BPS and BPF exposure decreased the number of corpora lutea, suggesting reduced ovulation rates. Moreover, BPA exposure increased male kidney and prostate gland weights, BPF decreased epididymal adipose tissue weights, and BPS had modest effects on male abdominal adipose tissue weights. Prenatal BPS exposure reduced anogenital distance (AGD) in male offspring, suggesting possible feminization, whereas both BPS and BPA induced oxidative stress in the testes. These results indicate that prenatal exposure to BPF affects pregnancy outcomes, BPS alters male AGD, and all three bisphenols alter certain organ weights in male offspring and ovarian function in female offspring. Altogether, it appears that prenatal exposure to BPA or its analogues can induce reproductive toxicity even at low doses.
本研究旨在评估低剂量双酚 A(BPA)、双酚 S(BPS)和双酚 F(BPF)对妊娠结局和后代发育的影响。妊娠 Sprague-Dawley 大鼠在妊娠第 6-21 天经口给予溶剂、5μg/kg 体重(BW)/天 BPA、BPS 和 BPF 或 1μg/kg BW/天 BPF。监测妊娠和妊娠结局,包括流产和死胎数量。雄性和雌性后代在出生时进行形态测量学检查,然后进行出生前和断奶后体重、断奶后食物和水摄入量以及成年器官重量检测。还从成年雌性后代中获得卵巢卵泡计数。我们观察到暴露于 5μg/kg BPF 的母鼠中有 80%以上发生自发性流产。BPA 暴露增加了雌性后代的格拉夫卵泡,而 BPS 和 BPF 暴露则减少了黄体数量,表明排卵率降低。此外,BPA 暴露增加了雄性肾脏和前列腺的重量,BPF 降低了附睾脂肪组织的重量,BPS 对雄性腹部脂肪组织的重量有一定影响。产前 BPS 暴露降低了雄性后代的肛门生殖器距离(AGD),提示可能出现女性化,而 BPS 和 BPA 均诱导了睾丸的氧化应激。这些结果表明,产前暴露于 BPF 会影响妊娠结局,BPS 改变了雄性 AGD,而所有三种双酚类物质均改变了雄性后代的某些器官重量和雌性后代的卵巢功能。总之,似乎产前暴露于 BPA 或其类似物即使在低剂量下也能引起生殖毒性。