Abstract

Medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system, similar to that of mammals. However, under high temperature conditions, XX medaka is masculinised by elevation of cortisol, the major teleost glucocorticoid. In this study, to identify novel factors in the gonads acting downstream from cortisol during sexual differentiation, we performed RNA sequencing (RNA-seq) analysis using the gonadal regions of larvae reared at normal temperature with and without cortisol, and at high temperature. The RNA-seq and real-time PCR analyses showed that expression of some peroxisome proliferator-activated receptor α (PPARα) signalling-targeted genes was increased by cortisol. PPARα agonist treatment induced masculinisation of XX medaka in some cases, and co-treatment of the agonist with cortisol further induced masculinisation, whereas treatment of pparaa knockout medaka with cortisol or the agonist did not induce masculinisation. This study provides the first evidence that PPARα is involved in environmental sex determination in vertebrates.

Highlights

  • Medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system, similar to that of mammals

  • To identify novel factors acting downstream from cortisol in the gonads during sexual differentiation, we performed RNA sequencing (RNA-seq) analysis using the gonadal regions of larvae treated with High temperature (HT) or cortisol

  • Real-time PCR analysis revealed that cortisol increased the expression levels of fabp728, ­apolipoprotein[29], and ucp[130], which are known to be peroxisome proliferator-activated receptor α (PPARα) signal-targeted genes containing the peroxisome proliferator response elements (PPREs) within the promoters, suggesting that cortisol activates the PPARα signalling pathway

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Summary

Introduction

Medaka (Oryzias latipes) is a teleost fish with an XX/XY sex determination system, similar to that of mammals. Sex is genotypically determined in many species, but sex determination is greatly affected by ambient temperature in poikilothermic vertebrates, including reptiles, amphibians, and f­ish[1] Environmental factors, such as p­ H2, ­density[3], and social f­actors[4], are suggested to override genetic sex determination in some teleost fish. Exposure of XX medaka to cortisol or HT increases expression of gonadal soma-derived growth factor (gsdf) and decreases expression of cytochrome P450 family 19 subfamily A member 1a (cyp19a1a) by 5 days post-hatching (dph)[16]. It remains unclear how HT-elevated cortisol induces the masculinisation of XX medaka. Glucocorticoids may have the potential to cause masculinisation in poikilothermic vertebrates

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