Department of Molecular and Environmental Bioscience, Graduate School, Hanyang University, Seoul 133-791, South Korea.
Aquat Toxicol. 2011 Aug;104(3-4):218-29. doi: 10.1016/j.aquatox.2011.04.020. Epub 2011 May 7.
Endocrine disrupting chemicals (EDCs) have been a major concern in the normal reproduction and development of aquatic organisms. In the teleost, steroid hormones are synthesized via the steroidogenesis pathway, and play a key physiological role in the regulation of gonadal sex differentiation. The protogynous hermaphroditic fish, Kryptolebias marmoratus is the only vertebrate capable of reproducing through internal self-fertilization. To uncover the effect of bisphenol A (BPA) on sex differentiation genes on transcription, we investigated the expression patterns of several sex differentiation-related genes such as dax1, dmrt1, mis, sf1, figlα, StAR and wt1 after BPA exposure with controls (E2 and TMX). In response to 17β-estradiol (E2) exposure, a testis-specific gene, dmrt1 mRNA was down-regulated in the gonad of the secondary male but the expression of the female-specific gene, dax1 mRNA was significantly elevated in the brain and gonad. A high level of StAR mRNA was detected in the brain and gonad of both hermaphrodite and secondary males, suggesting that the elevated expression of dax1 and StAR genes would be involved in E2 exposure. As expected, upon BPA exposure, the dmrt1 and MIS mRNA level decreased in both hermaphrodite and secondary males, while the female-specific gene, figlα mRNA level increased in the gonad of both genders. BPA showed an opposite mode of action on the expression of dax1 (induction, P>0.05) and sf1 mRNA (inhibition, P>0.05) in the brain and gonad against both genders. The sensitivity of dax1 to BPA on expression was relatively high in the secondary male. The wt1 mRNA was up-regulated in most tissues except in the liver of BPA-exposed secondary males. Regarding the time course study, the figlα mRNA level increased at 6 h after BPA exposure. In addition, BPA elevated the expression of StAR, dax1, and wt1 mRNA but repressed sf1 mRNA. In this paper, we demonstrated that BPA may modulate the expression of sex differentiation and steroidogenesis pathway genes, and this finding would provide a better understanding on the modulation of transcription upon BPA exposure in steroidogenesis and sex differentiation in the hermaphroditic fish, K. marmoratus.
内分泌干扰化学物质（EDCs）一直是水生生物正常繁殖和发育的主要关注点。在硬骨鱼中，类固醇激素通过类固醇生成途径合成，在调节性腺性别分化中发挥关键生理作用。雌雄同体的褐菖鲉是唯一能够通过内部自体受精繁殖的脊椎动物。为了揭示双酚 A（BPA）对转录过程中性别分化基因的影响，我们研究了几种性别分化相关基因的表达模式，如 dax1、dmrt1、mis、sf1、figlα、StAR 和 wt1，这些基因在 BPA 暴露后与对照组（E2 和 TMX）相比。在 17β-雌二醇（E2）暴露下，睾丸特异性基因 dmrt1mRNA 在次级雄性性腺中下调，但雌性特异性基因 dax1mRNA 在大脑和性腺中显著升高。高 StARmRNA 水平在两性的大脑和性腺中均有检测到，表明 dax1 和 StAR 基因的高表达可能参与 E2 暴露。正如预期的那样，在 BPA 暴露后，两性的 dmrt1 和 MISmRNA 水平均下降，而雌性特异性基因 figlαmRNA 水平在两性性腺中均升高。BPA 对两性大脑和性腺中 dax1（诱导，P>0.05）和 sf1mRNA（抑制，P>0.05）的表达表现出相反的作用模式。在次级雄性中，dax1 对 BPA 的敏感性相对较高。wt1mRNA 在大多数组织中上调，除了 BPA 暴露的次级雄性肝脏。关于时间过程研究，figlαmRNA 水平在 BPA 暴露后 6 小时增加。此外，BPA 上调了 StAR、dax1 和 wt1mRNA 的表达，但抑制了 sf1mRNA 的表达。在本文中，我们证明 BPA 可能调节性别分化和类固醇生成途径基因的表达，这一发现将有助于更好地理解 BPA 暴露对褐菖鲉类固醇生成和性别分化过程中转录的调节。
