title: Juvenile ovary to testis transition in zebrafish involves inhibition of ptges.
abstract: 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.
authors.affiliation: Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden.
authors.forename: Ajay
authors.initials: A
authors.lastname: Pradhan
authors.affiliation: Biology, The Life Science Center, School of Science and Technology, Örebro University, Örebro, Sweden per-erik.olsson@oru.se.
authors.forename: Per-Erik
authors.initials: PE
authors.lastname: Olsson
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000201:enzymology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D000077239:Meloxicam; D010053:Ovary / Q000201:enzymology / Q000502:physiology*; D015230:Prostaglandin D2 / Q000235:genetics / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D019849:Sex Determination Processes / Q000502:physiology*; D012744:Sex Ratio; D015398:Signal Transduction / Q000502:physiology; D013737:Testis / Q000201:enzymology / Q000254:growth & development*; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D015027:Zebrafish / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D055758:SOX9 Transcription Factor; C504918:Sox9a protein, zebrafish; D013843:Thiazines; D013844:Thiazoles; D029961:Zebrafish Proteins; D051176:beta Catenin; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605872:ptges protein, zebrafish; D015232:Dinoprostone; D015230:Prostaglandin D2; D000077239:Meloxicam
keywords: fish reproduction; gene expression; prostaglandins; sex determination; sex differentiation