Department of Biomedical Sciences, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
HGG Research LLC, Athens, GA, USA.
Neurotoxicology. 2021 Dec;87:156-166. doi: 10.1016/j.neuro.2021.09.006. Epub 2021 Sep 28.
The growing concern surrounding bisphenol A (BPA) has led to increased industrial production and application of its analog bisphenol S (BPS). The goals of this study were: (1) To examine the generational effects in the nematode C. elegans for up to three generations following developmental exposure to BPS (0.1, 1.0, 5.0 and 10.0 μM), and (2) To examine the neurotoxicity and metabolic toxicity in NODEF mouse offspring exposed to BPS (3 μg/kg BW) in utero throughout gestation once/day via oral pipette. First, worms were exposed to BPS developmentally for a single period of 48 hours and then propagated for 2 additional generations. Exposure to 0.1 and 1.0 μM BPS decreased lifespan and the number of progeny with an ability to recover in subsequent generations. In contrast, worms exposed to 5.0 or 10.0 μM BPS exhibited a continuous effect in the second generation, e.g., decreased lifespan and reduced number of progeny. Only worms exposed to 10.0 μM BPS continued to have a significant long-term effect (e.g., decreased lifespan) through the third generation. In addition, worms developmentally exposed to BPS at 5.0 μM and 10.0 μM also showed decreases in body bends. In contrast, worms exposed to 0.1 μM BPS exhibited a significant increase in head thrashes. When the multigenerational effects were examined by exposing worms to BPS for 48 hours developmentally at each generation for three generations, an accumulative effect was observed in worms treated with 0.1 or 1.0 μM BPS for two generations, but not for three generations, suggesting a threshold existed. Worms exposed to either 5.0 or 10.0 μM BPS demonstrated accumulative effects through two and three generations. When the developmental effects of BPS were studied in NODEF mice, offspring exposed gestationally exhibited behavioral deficits at 12, but not at 3, weeks of age. Specifically, female offspring had decreases in working and short-term memories while male offspring showed increases in hyperactivity and anxiety-like behaviors. In summary, this study demonstrates the sex-related effects of BPS in NODEF mouse offspring exposed in utero, along with the generational effects observed in C. elegans.
双酚 A（BPA）引发的担忧日益加剧，导致其类似物双酚 S（BPS）的工业生产和应用不断增加。本研究的目的是：（1）研究在秀丽隐杆线虫中，在发育过程中暴露于 BPS（0.1、1.0、5.0 和 10.0 μM）后，进行多达三代的代际效应，以及（2）研究在 NODEF 小鼠中，BPS（3μg/kg BW）经口管在整个孕期每天一次宫内暴露时的神经毒性和代谢毒性。首先，线虫在发育过程中仅暴露于 BPS 一次，持续 48 小时，然后再繁殖两代。暴露于 0.1 和 1.0 μM BPS 会降低寿命和具有在后代中恢复能力的后代数量。相比之下，暴露于 5.0 或 10.0 μM BPS 的线虫在第二代表现出连续效应，例如，寿命降低和后代数量减少。只有暴露于 10.0 μM BPS 的线虫在第三代仍表现出显著的长期影响（例如，寿命降低）。此外，在发育过程中暴露于 5.0 μM 和 10.0 μM BPS 的线虫的身体弯曲也减少了。相比之下，暴露于 0.1 μM BPS 的线虫的头部抽搐明显增加。当通过在每一代中发育性地暴露于 BPS 48 小时并持续三代来检查多代效应时，在两代中用 0.1 或 1.0 μM BPS 处理的线虫观察到累积效应，但在三代中没有观察到，这表明存在一个阈值。暴露于 5.0 或 10.0 μM BPS 的线虫在两代和三代中均表现出累积效应。当在 NODEF 小鼠中研究 BPS 的发育效应时，妊娠暴露的后代在 12 周而不是 3 周时表现出行为缺陷。具体而言，雌性后代的工作和短期记忆减少，而雄性后代表现出多动和焦虑样行为增加。总之，本研究表明，在宫内暴露于 BPS 的 NODEF 小鼠后代中观察到了 BPS 的性别相关效应，以及在秀丽隐杆线虫中观察到的代际效应。
