FERNANDINO Juan Ignacio
congresos y reuniones científicas
Corticotropin-releasing hormone as the transducer of the stress-induced masculinization.
CASTAÑEDA CORTÉS, D.C.; ARIAS PADILLA, L.F.; LANGLOIS, V.S.; SOMOZA, G.M.; FERNANDINO, J.I.
Congreso; IX LATIN AMERICAN SOCIETY FOR DEVELOPMENTAL BIOLOGY MEETING 2017; 2017
LATIN AMERICAN SOCIETY FOR DEVELOPMENTAL BIOLOGY
The exposure to environmental stressors during early development has important implications for the rescheduling of many cellular and molecular mechanisms. In fish, exposition to high temperatures (HT), or other stressors, increase cortisol levels, inducing gonadal masculinization, even in genotypic females. Corticotropin-releasing hormone (Crh), is considered the regulator of the hypothalamic-pituitary-adrenal/interrenal axis (HPA/I). Crh stimulates the secretion and release of the adrenocorticotropic hormone (Acth) in the pituitary. This latter hormone regulates cortisol levels via the adrenal/interrenal gland. In this context, we have proposed to determinate if HPA axis is active during sexual determination and differentiation period of Medaka fish (Oryzias latipes). In teleost fish, two crh ohnologs (crha and crhb) have been identified. In this study, crhb and its receptors (crhr1 and crhr2) presented high expression at HT, during a critical period in which the gonadal primordium is labile to sex-reversal. However, crha has not showed dimorphic expression between the temperature treatments in any development stage. To elucidate the regulation of HPA/I, we disrupted the axis through the loss of function of crh receptors (lof-crhr1 and lof-crhr2) using CRISPR/Cas9 system. We observed that lof-crhr1 and lof-crhr2 in genotypic female embryos reared at HT, showed a female pattern (low expression) of the gonadal soma derived factor (gsdf) a well know masculinization marker in Medaka. Interestingly, after the period of gonadal differentiation (post-embryonic stages), the mutations of crhr2, but not crhr1, on genetic female embryos exposed to HT prevent gonadal masculinization. We found that masculinization in the lof-crhr1 larvae could be explained by a compensatory molecular mechanism by the crhr2. Furthermore, immunodetection of Acth suggests that the prevention of masculinization in lof-crhr2, it is due to the lack of Acth release by the pituitary. Finally, we could rescue the sex reversal induced by HT in crhr2 mutants by the addition of cortisol, the downstream effector of the HPA/I axis. In summary, our results revealed the importance of the HPA/I axis as the transducer of stress-induced masculinization on genetic females. This work highlights the importance of crhb, and their receptors, in the sex reversal.