State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; Ningxia Medical University, Yinchuan, Ningxia 750004, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China.
Ecotoxicol Environ Saf. 2022 May 1;236:113453. doi: 10.1016/j.ecoenv.2022.113453. Epub 2022 Apr 4.
There is growing concern about adverse effects of bisphenol A alternatives including bisphenol B (BPB) due to their estrogenic activity. However, limited data are available concerning the influences of BPB on male reproductive development in vertebrates, especially in amphibians, which are believed to be susceptible to estrogenic chemicals. The present study investigated the effects of 10, 100 and 1000 nM BPB (2.42, 24.2 and 242 μg/L) on testis development in Xenopus laevis, a model amphibian species for studying gonadal feminization. We found that exposure to BPB from stages 45/46 to 52 resulted in down-regulation of testis-biased gene expression and up-regulation of ovary-biased gene and vitellogenin (vtgb1) expression in gonad-mesonephros complexes (GMCs) of tadpoles at stage 52, coupled with suppressed cell proliferation in testes and reduced gonadal metameres, resembling the effects of 17ß-estradiol. Moreover, an estrogen receptor (ER) antagonist ICI 182780 antagonized BPB-caused up-regulation of ovary-biased gene and vtgb1 expression to some degree, indicating that the effects of BPB on X. laevis testis differentiation could be partly mediated by ER. All observations demonstrate that early exposure to BPB inhibited testis differentiation and exerted certain feminizing effects during gonadal differentiation. When exposure was extended to post-metamorphosis, testes exhibited histological and morphological abnormalities including segmented, discontinuous and fragmented shapes, besides altered sex-dimorphic gene expression. Notably, most of BPB-caused alterations were not concentration-dependent, but the lowest concentration indeed exerted significant effects. Overall, our study for the first time reveals that low concentrations of BPB can disrupt testis differentiation partly due to its estrogenic activity and subsequently cause testicular dysgenesis after metamorphosis, highlighting its reproductive risk to amphibians and other vertebrates including humans. Our finding also implies that estrogenic chemicals-caused testis differentiation inhibition at tadpole stages could predict later testicular dysgenesis after metamorphosis, meaning a possibility of early detection of abnormal testis development caused by estrogenic chemicals.
人们越来越关注双酚 A 替代品（包括双酚 B，BPB）的不良影响，因为它们具有雌激素活性。然而，关于 BPB 对脊椎动物，尤其是对被认为易受雌激素类化学物质影响的两栖动物雄性生殖发育的影响，相关数据有限。本研究以非洲爪蟾（Xenopus laevis）为模型，探讨了从 45/46 期到 52 期接触 BPB（2.42、24.2 和 242μg/L）对其睾丸发育的影响。结果显示，BPB 暴露导致 52 期时性腺-中肾复合物（GMC）中睾丸偏向基因的表达下调和卵巢偏向基因和卵黄蛋白原 1（vtgb1）的表达上调，同时睾丸细胞增殖受到抑制，生殖节减少，与 17β-雌二醇的作用相似。此外，雌激素受体（ER）拮抗剂 ICI 182780 部分拮抗了 BPB 引起的卵巢偏向基因和 vtgb1 表达的上调，表明 BPB 对非洲爪蟾睾丸分化的影响部分可通过 ER 介导。所有观察结果表明，早期接触 BPB 可抑制睾丸分化，并在生殖分化过程中产生一定的雌性化作用。当暴露延伸到变态后，睾丸表现出组织学和形态学异常，包括分段、不连续和碎片化的形状，以及性别二态性基因表达的改变。值得注意的是，BPB 引起的大部分改变与浓度无关，而是最低浓度确实产生了显著影响。总的来说，本研究首次表明，低浓度的 BPB 可通过其雌激素活性部分干扰睾丸分化，并在变态后导致睾丸发育不良，突显其对两栖动物和包括人类在内的其他脊椎动物的生殖风险。我们的发现还表明，在蝌蚪阶段由于雌激素类化学物质引起的睾丸分化抑制可能预示着变态后睾丸发育不良，这意味着可以早期检测到雌激素类化学物质引起的睾丸发育异常。
