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Development. 2019 Apr 23;146(8). pii: dev172866. doi: 10.1242/dev.172866.

The central nervous system acts as a transducer of stress-induced masculinization through corticotropin-releasing hormone B.

Author information

1
Laboratorio de Biología del Desarrollo - Instituto Tecnológico de Chascomús, INTECH (CONICET-UNSAM), Chascomús B7130IWA, Argentina.
2
Institut National de la Recherche Scientifique (INRS) - Centre Eau Terre Environnement, Quebec G1K 9A9, Canada.
3
Laboratorio de Ictiofisiología y Acuicultura - INTECH (CONICET-UNSAM), Chascomús B7130IWA, Argentina.
4
Laboratorio de Biología del Desarrollo - Instituto Tecnológico de Chascomús, INTECH (CONICET-UNSAM), Chascomús B7130IWA, Argentina fernandino@intech.gov.ar.

Abstract

Exposure to environmental stressors, such as high temperature (HT), during early development of fish induces sex reversal of genotypic females. Nevertheless, the involvement of the brain in this process is not well clarified. In the present work, we investigated the mRNA levels of corticotropin-releasing hormone b (crhb) and its receptors (crhr1 and crhr2), and found that they were upregulated at HT during the crucial period of gonadal sex determination in medaka. In order to clarify their roles in sex reversal, biallelic mutants for crhr1 and crhr2 were produced by CRISPR/Cas9 technology. Remarkably, biallelic mutants of both loci (crhr1 and crhr2) did not undergo female-to-male sex reversal upon exposure to HT. Inhibition of this process in double corticotropin-releasing hormone receptor mutants could be successfully rescued through the administration of the downstream effector of the hypothalamic-pituitary-interrenal axis, cortisol. Taken together, these results reveal for the first time that the CNS acts as a transducer of masculinization induced by thermal stress.

KEYWORDS:

CRH; CRISPR/Cas9; Environmental stress; Masculinization; Medaka

PMID:
30936180
DOI:
10.1242/dev.172866

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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