242 | Role of neonatal sex differences in DNA demethylation in the organizational effects of testosterone

Neuroendocrinology and Neuroimmunology

Author: Rocio del Milagro Bigarani | Email: robigarani@mi.unc.edu.ar

Rocio Bigarani , Maria Julia Cambiasso , Carla Daniela Cisternas

1° 1Instituto de Investigación Médica M y M Ferreyra, INIMEC-CONICET-UNC, Córdoba, Argentina.

Sex differences in neurochemical cell phenotype may have broad consequences and underlie differences in neural function, morphology, connectivity, and neurotransmitter production in males and females. Recent studies have shown that the expression of enzymes that place or remove DNA methylation marks is greatest in the first week of life, overlaps with the perinatal critical period of sexual differentiation and a neonatal inhibition of DNA methylation or demethylation abolishes sex differences in cell phenotype. Here, we explored how early sex differences in gene expression of TET 1-2-3, GADD45a-b and TDG (involved in the removal of 5-methylcytosine) may correlate with gene expression of oxytocin (OXT) and the oxytocin (OT) receptor (R) in specific regions of the mouse brain. mRNA expression was evaluated by qPCR in brain punches of prefrontal cortex (PFC), preoptic area (POA) and the paraventricular nucleus of the hypothalamus (PVN) at postnatal day (P) 7 and 18-19. In PFC, we found sex differences (males>females) in TET1-2-3, TDG and Gadd45a-b expressions and a higher OTR-expression in males at P7(p<0.05). We also evaluated OT expression by immunohistochemistry at P18-19 in the POA, PVN and the supraoptic nucleus of the hypothalamus and found higher expression in female POA. Overall, these results suggest that a sex-specific pattern of active DNA demethylation machinery during neonatal life could underline the organizational effects of hormones on neurochemical phenotype.