Oxidative Stress Causes Masculinization of Genetically Female Medaka Without Elevating Cortisol

Abstract

Medaka (Oryzias latipes) 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 via 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 (H2O2), which induces oxidative stress in vertebrates. H2O2 treatment from 0 to 5 days post-hatching induced masculinization of wild-type XX medaka, but not of gonadal soma-derived growth factor (gsdf) or peroxisome proliferator-activated receptor alpha-a (pparaa) knockout XX fish. Co-treatment with an oxidative stress inhibitor caused masculinization recovery but co-treatment with a cortisol synthesis inhibitor did not. H2O2 treatment significantly upregulated gsdf and pparaa expression in XX medaka. However, H2O2 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.

Temperature- and chemical-induced neurotoxicity in zebrafish

“…Cortisol plays a pivotal role in the response to stressful conditions, also influencing the functioning of mitochondria ( Roosevelt et al, 1973 ; Picard and McEwen, 2018 ) ( Figure 2L ) and oxidative stress ( Nakano et al, 2014 ; Espinoza et al, 2017 ; Mukai et al, 2022 ) ( Figure 2M ).…”

Does stress make males? An experiment on the role of glucocorticoids in anuran sex reversal

“…Arriving at the conclusion that CORT did not drive sex reversal in agile frogs, we can speculate that the proximate mechanism of ESD in amphibians may be something else than the glucocorticoid pathway supported in fishes. Proposed alternative mechanisms (none of which are mutually exclusive) are the cellular calcium and redox regulation [16,47], epigenetic processes [18,48], thyroid hormones [15,20,49], and the energy limitation hypothesis [14]. The latter proposes that nutritional stress via lipid and carbohydrate metabolism pathways serves as signal transducer between environment and sex.…”

Does stress make males? An experiment on the role of glucocorticoids in anuran sex reversal

“…Proposed alternative mechanisms (none of which are mutually exclusive) are the cellular calcium and redox regulation (Castelli et al, 2020;Mukai et al, 2022), epigenetic processes (Shao et al, 2014;Zhang et al, 2022), thyroid hormones (Castañeda-Cortés & Fernandino, 2021;Hayes, 1998;Sun et al, 2016), and the energy limitation hypothesis (Geffroy, 2022).…”

“…Arriving at the conclusion that CORT did not drive sex reversal in agile frogs, we can speculate that the proximate mechanism of environmentally sensitive sex determination in amphibians may be something else than the glucocorticoid pathway supported in fishes. Proposed alternative mechanisms (none of which are mutually exclusive) are the cellular calcium and redox regulation (Castelli et al, 2020; Mukai et al, 2022), epigenetic processes (Shao et al, 2014; Zhang et al, 2022), thyroid hormones (Castañeda‐Cortés & Fernandino, 2021; Hayes, 1998; Sun et al, 2016), and the energy limitation hypothesis (Geffroy, 2022). The latter proposes that nutritional stress via lipid and carbohydrate metabolism pathways serves as signal transducer between environment and sex.…”