Abstract

Retinoic Acid (RA) is a vitamin A derivative present in many biological processes including embryogenesis, organ development and cell differentiation. The RA signaling pathway is essential for the onset of meiosis in tetrapods, although its role in fish reproduction needs further evidence. This study reports the expression profiles of several genes involved in this pathway during sex differentiation and the first reproductive season in European sea bass (Dicentrarchus labrax) gonads. The assessed genes are representative of several steps of the pathway including retinol transport, RA synthesis, nuclear receptors, RA transport and degradation. The study includes a synteny analysis of stra8, a tetrapod meiosis gatekeeper, in several taxa. The results show that, these genes were overexpressed during early gonad development and their expression decreased during meiosis progression in males and during vitellogenesis in females. Specifically, a decrease of cyp26a1, involved in RA degradation, together with an increase of aldh1a2 and aldh1a3, in charge of RA-synthesis, might ensure the availability of high RA levels at the time of meiosis in males and females. Moreover, the absence of stra8 in the European sea bass genome, as well as the conserved genomic neighbourhood found in other taxa, suggest a stra8 independent signaling for RA during meiosis. Taken together, our results might help to better understand the role of RA signaling in teleost gonad development.

Highlights

  • Retinoic acid (RA) is the active form of vitamin A, and exerts pleiotropic functions in many biological processes such as differentiation of the nervous system (McCaffery et al, 2003), embryogenesis (Reijntjes et al, 2004), body patterning (Marill et al, 2003), organ and skeletal development (Campo-Paysaa et al, 2008; Spoorendonk et al, 2008) or cell differentiation (Niederreither and Dolle, 2008)

  • The present study shows that the highest expression levels of nuclear receptors occur right before the onset of meiosis in males, while in females, the increase during meiosis resumption is only true for pparg

  • Synthesis, transport, and signaling. cyp26a1 levels are kept high in order to prevent an early entry into meiosis, in agreement with the role of this enzyme as the meiosis inhibiting factor in vertebrates

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Summary

Introduction

Retinoic acid (RA) is the active form of vitamin A, and exerts pleiotropic functions in many biological processes such as differentiation of the nervous system (McCaffery et al, 2003), embryogenesis (Reijntjes et al, 2004), body patterning (Marill et al, 2003), organ and skeletal development (Campo-Paysaa et al, 2008; Spoorendonk et al, 2008) or cell differentiation (Niederreither and Dolle, 2008). More than a century of research has built up a solid framework concluding that the RA signaling pathway is essential for the onset of meiosis in tetrapods (Griswold et al, 2012). This pathway involves the initial formation of a complex for retinol (ROL) bloodstream transport, which includes the ROL binding protein-4 (Rbp). ROL can either remain bound to Stra, or be transformed into RA by two tandem oxidations. RA is highly unstable and toxic and can either bind to an intracellular protein (Crabp), in order to keep it soluble, or be degraded by Cyp enzymes into more polar compounds easier to clear out from the cell (Thatcher and Isoherranen, 2009)

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