Retinoic acid homeostasis through aldh1a2 and cyp26a1 mediates meiotic entry in Nile tilapia (Oreochromis niloticus)

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...

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Bibliographic Details
Published in:Scientific reports 2015-05, Vol.5 (1), p.10131-10131, Article 10131
Main Authors: Feng, Ruijuan, Fang, Lingling, Cheng, Yunying, He, Xue, Jiang, Wentao, Dong, Ranran, Shi, Hongjuan, Jiang, Dongneng, Sun, Lina, Wang, Deshou
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Cichlids - growth & development
CRISPR
Cytochrome P-450 Enzyme System - biosynthesis
Cytochrome P-450 Enzyme System - genetics
Disorders of Sex Development - chemically induced
Enzymes
Estrogens - pharmacology
Fadrozole - pharmacology
Fish
Gene Expression Regulation, Developmental - drug effects
Germ cells
Homeostasis
Meiosis
Meiosis - genetics
Ovaries
Retinal Dehydrogenase - antagonists & inhibitors
Retinal Dehydrogenase - genetics
Retinoic acid
Retinoic Acid 4-Hydroxylase
Reversion
Sex determination
Sex Determination Processes - drug effects
Sex Determination Processes - genetics
Sex reversal
Signal transduction
Synaptonemal Complex - metabolism
Tilapia
Tretinoin - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep10131