Pradhan Ajay, Olsson Per-Erik
Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden.
Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden
Biol Reprod. 2014 Aug;91(2):33. doi: 10.1095/biolreprod.114.119016. Epub 2014 Jun 11.
The sex differentiation mechanisms in zebrafish (Danio rerio) remains elusive, partly because of the absence of sex chromosomes but also because the process appears to depend on the synchrony of multiple genes and possibly environmental factors. Zebrafish gonadal development is initiated through the development of immature oocytes. Depending on multiple signaling cues, in about half of the individuals, the juvenile ovaries degenerate or undergo apoptosis to initiate testes development while the other half maintains the oogenic pathway. We have previously shown that activation of NFκB and prostaglandin synthase 2 (ptgs2) results in female-biased sex ratios. Prostaglandin synthase and prostaglandins are involved in multiple physiological functions, including cell survival and apoptosis. In the present study, we show that inhibition of ptgs2 by meloxicam results in male-biased sex ratios. On further evaluation, we observed that exposure with the prostaglandin D2 (PGD2) analogue BW-245C induced SRY-box containing gene 9a (sox9a) and resulted in male-biased sex ratios. On the other hand, prostaglandin E2 (PGE2) treatment resulted in female-biased sex ratios and involved activation of NFκB and the β-catenin pathway as well as inhibition of sox9. Exposure to the β-catenin inhibitor PNU-74654 resulted in up-regulation of ptgds and male-biased sex ratios, further confirming the involvement of β-catenin in the female differentiation pathway. In this study, we show that PGD2 and PGE2 can program the gonads to either the testis or the ovary differentiation pathways, indicating that prostaglandins are involved in the regulation of zebrafish gonadal differentiation.
斑马鱼（Danio rerio）的性别分化机制仍然难以捉摸，部分原因是缺乏性染色体，还因为这个过程似乎取决于多个基因的同步性以及可能的环境因素。斑马鱼性腺发育通过未成熟卵母细胞的发育启动。根据多种信号线索，在大约一半的个体中，幼年卵巢退化或发生凋亡以启动睾丸发育，而另一半则维持卵子发生途径。我们之前已经表明，NFκB和前列腺素合酶2（ptgs2）的激活会导致雌性偏向的性别比例。前列腺素合酶和前列腺素参与多种生理功能，包括细胞存活和凋亡。在本研究中，我们表明美洛昔康对ptgs2的抑制导致雄性偏向的性别比例。进一步评估时，我们观察到用前列腺素D2（PGD2）类似物BW - 245C处理会诱导含SRY盒基因9a（sox9a）并导致雄性偏向的性别比例。另一方面，前列腺素E2（PGE2）处理导致雌性偏向的性别比例，并且涉及NFκB和β - 连环蛋白途径的激活以及sox9的抑制。暴露于β - 连环蛋白抑制剂PNU - 74654会导致ptgds上调和雄性偏向的性别比例，进一步证实了β - 连环蛋白参与雌性分化途径。在本研究中，我们表明PGD2和PGE2可以使性腺向睾丸或卵巢分化途径编程，表明前列腺素参与斑马鱼性腺分化的调节。
