PT  - JOURNAL ARTICLE
AU  - DC Castañeda Cortés
AU  - LF Arias Padilla
AU  - VS Langlois
AU  - GM Somoza
AU  - JI Fernandino
TI  - The Central Nervious System Acts as a Transducer of Stress-Induced Masculinization through Corticotropin-Releasing Hormone B
AID  - 10.1101/415554
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 415554
4099  - http://biorxiv.org/content/early/2018/09/14/415554.short
4100  - http://biorxiv.org/content/early/2018/09/14/415554.full
AB  - Exposure to environmental stressors during early development has important implications for rescheduling many cellular and molecular mechanisms. In some fish species, environmental stressors, like high temperatures (HT), cause an increase in cortisol levels. In turn, this mechanism induces sex reversal of genotypic females, overriding genetic factors related to development of the gonad. However, 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 out that they were up-regulated at HT during the critical period of gonadal sex determination in medaka (Oryzias latipes), i.e., when the gonadal primordium is sexually labile. In order to clarify their roles in sex reversal, biallelic mutants for crhr1 and crhr2 were produced by CRISPR/Cas9 technology. Remarkably, biallelic mutant of both loci (crhr1 and crhr2) did not undergo female-to-male sex reversal upon HT exposition, whereas mutants for either crhr1 or crhr2 showed partial, or intersex phenotypes, suggesting that both crh receptors are required for HT-induced masculinization. Inhibition of this process in double crhrs mutants could be successfully rescued through the administration of the downstream effector of the hypothalamic-pituitary interrenal axis, the cortisol. Taken together, these results revealed for the first time the participation of the central nervous system acting as a transducer of masculinization induced by thermal stress.