Starvation causes female-to-male sex reversal through lipid metabolism in the teleost fish, medaka (Olyzias latipes).

Yuta Sakae,Yuki Sugiura,Toshiya Nishimura,Minoru Tanaka,Shuhei Nakamura,Masatoshi Mita,Akira Oikawa,Makoto Suematsu

doi:10.1242/bio.050054

Abstract

ABSTRACTThe teleost fish, medaka (Oryzias latipes), employs the XX/XY genetic sex determination system. We show here that the phenotypic sex of medaka is affected by changes in lipid metabolism. Medaka larvae subjected to 5 days of starvation underwent female-to-male sex reversal. Metabolomic and RT-qPCR analyses indicated that pantothenate metabolism was suppressed by starvation. Consistently, inhibiting the pantothenate metabolic pathway caused sex reversal. The final metabolite in this pathway is coenzyme A, an essential factor for lipogenesis. Inhibiting fatty acid synthesis, the first step of lipogenesis, also caused sex reversal. The expression of dmrt1, a critical gene for male development, was suppressed by starvation, and a dmrt1 (Δ13) mutant did not show sex reversal under starvation. Collectively, these results indicate that fatty acid synthesis is involved in female-to-male sex reversal through ectopic expression of male gene dmrt1 under starvation.

Highlights

Medaka (Olyzias latipes) is a small model organism that employs the XX/XY genetic sex determination system (Aida, 1921; Matsuda and Sakaizumi, 2016)
Two different metabolomic analyses and pharmacological treatments revealed that pantothenate metabolism and fatty acid synthesis are involved in sex reversal through the expression of the male-development gene dmrt1
Starvation causes female-to-male sex reversal We first determined the growth of medaka larvae under starvation conditions

Summary

INTRODUCTION

Medaka (Olyzias latipes) is a small model organism that employs the XX/XY genetic sex determination system (Aida, 1921; Matsuda and Sakaizumi, 2016). High water temperature and cortisol treatment reportedly induced female-to-male sex reversal. Fatty acid synthesis is the first step in de novo lipogenesis, and is a pathway for synthesizing saturated fatty acids ranging from butyric acid (4:0) to palmitic acid (16:0) by increasing the number of carbon chains in steps of two using malonyl Coenzyme A (CoA) and acetyl CoA as raw materials This reaction is catalyzed by fatty acid synthase (FAS). We have found that starvation during sex differentiation caused female-to-male sex reversal in medaka. Two different metabolomic analyses and pharmacological treatments revealed that pantothenate metabolism and fatty acid synthesis are involved in sex reversal through the expression of the male-development gene dmrt. Our results highlight an example of how the environment affects sex differentiation by triggering an internal metabolic change

RESULTS

DISCUSSION

MATERIALS AND METHODS