Implications of thyroid hormone axis on the stress-induced sex reversal.

CASTAÑEDA CORTÉS, D.C.; ZHANG, Y.; LANGLOIS, V.S.; FERNANDINO, J.I.

Taller; IV Taller Biología Celular y del Desarrollo; 2018

The participation of thyroid hormones (THs) in reproduction has recently taken a great interest. How-ever, the participation and regulation of THs in early gonadal development, and the cross talk with other axes, such as stress or gonadal axes, is far from being clarified. Recent studies in fish showed that exposure to thyroid hormones (THs) can induced the female-to-male sex reversal. Firstly we evaluated if the exposure of Tri-iodothyronine (T3) can induce the masculinization of genetic female of medaka (Oryzias latipes). A low percentage of sex reversal was found in treatments with T3; however, the expression of genes related with gonadal masculinization and THs pathways were up-regulated, showing that THs can modulate the gonadal axis. On the other hand, in non-mammalian species corti-cotropin-releasing hormone (CRH) can induce pituitary thyroid-stimulating hormone (TSH) secretion through the CRH type 2 receptor (CRHR2) expressed on pituitary thyrotrope cells, linking the stress and thyroid endocrine axes. To study the crosstalk between stress and thyroid axes we performed a medaka cDNA microarray after exposure embryos during the gonadal sex determination period to high temperature (stress treatment). 474 differentially expressed candidate genes were identified, observing that the both axes are together up-regulated, e.i. TSH, and the crhr1 and crhr2 are up-regulated in embryos under stress treatment. To corroborate the participation of TSH in the stress-induced sex reversal we performed biallelic mutant embryos for both crhrs by CRISPR/Cas9 and then were exposed to high temperature stress. In the biallelic crhrs mutants the tsh level was low, comparing with embryos wild type incubated at high temperature, phenocoping the control group incubated at normal temperature. In this study we provide evidences of the crosstalk between stress and THs axes in the stress-induced female-to-male sex reversal.