Chongqing Key Laboratory of Animal Biology, College of Life Sciences, Chongqing Normal University, Chongqing 401331, China.
Chongqing Key Laboratory of Animal Biology, College of Life Sciences, Chongqing Normal University, Chongqing 401331, China.
Environ Pollut. 2019 Jan;244:486-494. doi: 10.1016/j.envpol.2018.10.079. Epub 2018 Oct 18.
Environmental estrogens are capable of interfering with the spermatogenesis and fertility of fish. However in natural waters, these chemicals are more likely to occur as a combination rather than a single stressor. Whether and how the mixture of xenoestrogens with environmental relevant concentrations may affect fish spermatogenesis remains largely unknown. In this study, male zebrafish adults were administered to 17alpha-ethinylestradiol (EE2) and a mixture of xenoestrogens (Mix (E2, EE2, DES, 4-t-OP, 4-NP and BPA)), with the estrogenic potency equivalent to EE2. After a 60-day exposures, elevated mRNA levels of vitellogenin 1 (vtg1) and estrogen receptor 1 (esr1) in the liver of fish in both treated groups were observed. Moreover, the plasma level of E2 declined significantly in the Mix group and the ratio of 11-KT/E2 was significantly elevated in both treated groups. Consistently, the mRNA level of P450 side-chain cleavage (scc) in the EE2 group and ovarian type aromatase (cyp19a1a) in the Mix group was significantly suppressed. In addition, decreased gonadosomatic index and sperm count in the fish of Mix group were present. Furthermore, increased number of the proliferating germ cells (such as spermatogonia and spermatocytes) was observed in the fish of both groups, suggesting a stimulated germ cell proliferation and meiosis. Accordingly, both exposures significantly up-regulated the mRNA levels of genes in mitosis (cyclinb1) and meiosis (cyp26a1 in EE2 group, aldh1a2, cyp26a1, sycp3 and spo11 in Mix). In addition, decreased number of spermatozoa and increased number of TUNEL-positive signals were present in the testis of fish in the Mix group, indicating an enhanced apoptosis. Further analyses demonstrated the significant elevated expressions of tnfrsf1a and the ratio of tnfrsf1a/tnfrsf1b in the Mix group, suggesting an elevated apoptosis in the testis of fish in the Mix group via extrinsic pathway. The present study greatly extends our understanding of the underlying mechanisms of the reproductive toxicity of xenoestrogens on fish.
环境雌激素能够干扰鱼类的精子发生和生育能力。然而，在天然水中，这些化学物质更可能以组合的形式存在，而不是单一的胁迫因素。在环境相关浓度下，混合的外源性雌激素是否以及如何影响鱼类精子发生仍然知之甚少。在这项研究中，雄性斑马鱼成年鱼被给予 17α-乙炔基雌二醇（EE2）和混合外源性雌激素（Mix（E2、EE2、DES、4-t-OP、4-NP 和 BPA）），其雌激素效价相当于 EE2。在 60 天的暴露后，在两个处理组的鱼肝脏中，卵黄蛋白原 1（vtg1）和雌激素受体 1（esr1）的 mRNA 水平升高。此外，Mix 组血浆中 E2 水平显著下降，两组血浆中 11-KT/E2 比值显著升高。一致地，EE2 组 P450 侧链裂解（scc）和 Mix 组卵巢型芳香化酶（cyp19a1a）的 mRNA 水平显著受抑制。此外，Mix 组鱼的性腺指数和精子计数下降。此外，在两组鱼中观察到增殖性生殖细胞（如精原细胞和精母细胞）数量增加，提示生殖细胞增殖和减数分裂受到刺激。因此，两种暴露都显著上调了有丝分裂（cyclinb1）和减数分裂（EE2 组的 cyp26a1、aldh1a2、cyp26a1、sycp3 和 spo11）中基因的 mRNA 水平。此外，Mix 组鱼睾丸中的精子数量减少，TUNEL 阳性信号增多，提示凋亡增加。进一步分析表明，Mix 组 tnfrsf1a 的表达显著上调，tnfrsf1a/tnfrsf1b 的比值升高，提示 Mix 组鱼睾丸凋亡通过外源性途径增加。本研究极大地扩展了我们对环境雌激素对鱼类生殖毒性的潜在机制的理解。
