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Histone deacetylase gene expression is regulated by sex chromosome complement in the amygdala of the developing mouse brain

Camila Sosa

  • Córdoba,
  • Argentina
  • Camila Sosa ¹
  • , Carla D Cisternas ¹𝄒²𝄒³
  • , Romina Conti ²
  • , María Julia Cambiasso ¹𝄒²
  • 1 Instituto de Investigación Médica Mercedes y Martín Ferreyra
  • 2 Cátedra de Biología Celular, Facultad de Odontología, Universidad Nacional de Córdoba, Córdoba, Argentina.
  • 3 Cátedra de Fisiología Animal, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Argentina.

Sexual differentiation of the rodent brain depends mainly on the action of androgens secreted by the fetal testis during the perinatal “critical period” (E17-P10). Recently, the role of genetic factors derived from sex chromosome complement has been recognized. Both hormonal and genetic factors interact to induce long lasting effects on sexually dimorphic gene expression. Epigenetic histone modifications have emerged as mechanisms of regulation and maintenance of hormonal-dependent effects in the brain and histone deacetylation induced by histone deacetylases (Hdacs) has recently been implicated in brain masculinization. To analyse the contribution of sex chromosome complement on this process, we evaluated the expression of Class I and II Hdacs in E15 amygdala derived from the “Four Core Genotypes” mouse model which comprises XX and XY gonadal males and XX and XY gonadal females. The mRNA expression of Class I Hdac1, 2 and 8 as well as Class II Hdac4 and 6 in amygdalae was analyzed by qPCR. Hdac1, 2 and 8 expression levels were higher in amygdala derived from XX embryos compared to XY, irrespectively of gonadal sex. No differences were observed in Hdac4 and 6. Our results suggest that sex chromosomes may determine a sexually dimorphic gene expression through Class I Hdacs in specific areas of the mouse brain before the in utero exposure to gonadal hormones. Current experiments are evaluating candidate genes regulated by Class I Hdacs relevant to sexual differentiation.

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