AUTHOR=Mukai Koki , Hara Seiji , Sakima Konosuke , Nozu Ryo , Yazawa Takashi , Kitano Takeshi 

TITLE=Oxidative Stress Causes Masculinization of Genetically Female Medaka Without Elevating Cortisol

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.878286

DOI=10.3389/fendo.2022.878286

ISSN=1664-2392

ABSTRACT=<p>Medaka (<italic>Oryzias latipes</italic>) is a teleost fish with an XX/XY sex determination system. Sex reversal from female-to-male (masculinization of XX fish) can be induced through cortisol elevation from exposure to environmental stress such as high temperature during sexual differentiation. However, the effects of oxidative stress, generated <italic>via</italic> metabolic reactions and biological defense mechanisms, on the sexual differentiation of medaka are unclear. Here, we investigated the effect of oxidative stress on medaka sexual differentiation using hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), which induces oxidative stress in vertebrates. H<sub>2</sub>O<sub>2</sub> treatment from 0 to 5 days post-hatching induced masculinization of wild-type XX medaka, but not of gonadal soma-derived growth factor (<italic>gsdf</italic>) or peroxisome proliferator-activated receptor alpha-a (<italic>pparaa</italic>) knockout XX fish. Co-treatment with an oxidative stress inhibitor caused masculinization recovery but co-treatment with a cortisol synthesis inhibitor did not. H<sub>2</sub>O<sub>2</sub> treatment significantly upregulated <italic>gsdf</italic> and <italic>pparaa</italic> expression in XX medaka. However, H<sub>2</sub>O<sub>2</sub> did not elevate cortisol levels in medaka larvae during sexual differentiation. These results strongly indicate that oxidative stress induces masculinization of XX medaka without causing elevation of cortisol.</p>