title: Retinoic acid homeostasis through aldh1a2 and cyp26a1 mediates meiotic entry in Nile tilapia (Oreochromis niloticus).
abstract: Meiosis is a process unique to the differentiation of germ cells. Retinoic acid (RA) is the key factor controlling the sex-specific timing of meiotic initiation in tetrapods; however, the role of RA in meiotic initiation in teleosts has remained unclear. In this study, the genes encoding RA synthase aldh1a2, and catabolic enzyme cyp26a1 were isolated from Nile tilapia (Oreochromis niloticus), a species without stra8. The expression of aldh1a2 was up-regulated and expression of cyp26a1 was down-regulated before the meiotic initiation in ovaries and in testes. Treatment with RA synthase inhibitor or disruption of Aldh1a2 by CRISPR/Cas9 resulted in delayed meiotic initiation, with simultaneous down-regulation of cyp26a1 and up-regulation of sycp3. By contrast, treatment with an inhibitor of RA catabolic enzyme and disruption of cyp26a1 resulted in earlier meiotic initiation, with increased expression of aldh1a2 and sycp3. Additionally, treatment of XY fish with estrogen (E2) and XX fish with fadrozole led to sex reversal and reversion of meiotic initiation. These results indicate that RA is indispensable for meiotic initiation in teleosts via a stra8 independent signaling pathway where both aldh1a2 and cyp26a1 are critical. In contrast to mammals, E2 is a major regulator of sex determination and meiotic initiation in teleosts.
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Feng
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Fang
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Yunying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Ranran
authors.initials: R
authors.lastname: Dong
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Dongneng
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: Key Laboratory of Freshwater Fish Reproduction and Development (Ministry of Education), Key Laboratory of Aquatic Science of Chongqing, School of Life Science, Southwest University, 400715, Chongqing, P.R. China.
authors.forename: Deshou
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D023681:Cichlids / Q000254:growth & development*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics*; D012734:Disorders of Sex Development / Q000139:chemically induced*; D004967:Estrogens / Q000494:pharmacology; D017316:Fadrozole / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008540:Meiosis / Q000235:genetics; D050697:Retinal Dehydrogenase / Q000037:antagonists & inhibitors / Q000235:genetics*; D000072516:Retinoic Acid 4-Hydroxylase; D019849:Sex Determination Processes / Q000187:drug effects / Q000235:genetics; D013573:Synaptonemal Complex / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D004967:Estrogens; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D050697:Retinal Dehydrogenase; D017316:Fadrozole