Morphological Sex Reversal in the Sexually Dimorphic Nucleus of the Preoptic Area in the Hypothalamus Delineated by Calbindin D28k-Immunoreactive Cell Clusters in Y POS mice.

Sex-determining region Y (Sry) triggers testis development in mammals, and the presence or absence of testicular secretion determines their sex-specific brain phenotype. Mice with Y chromosome replaced by that of Mus domesticus poschiavinus (Y POS ) frequently display sex reversal due to delayed Sry expression. However, brain sexual dimorphism under conditions of disorders of sex development remains unclear. Here, we report sex differences in the sexually dimorphic nucleus of the preoptic area, delineated by cells positive for calbindin D28k, a male-predominant neuronal marker (CALB-SDN), in Y POS mice. The mice were divided into females and males according to gonadal phenotype. Cells immunoreactive (ir) for calbindin D28k (CALB) were more extensively distributed in male Y POS mice, compared with females. The CALB-ir cell numbers in the CALB-SDN were significantly higher in Y POS males than in Y POS females, which had numbers comparable to wild type females. No left-right differences in CALB-ir cell numbers were observed in the CALB-SDN. Collectively, these results demonstrate that sexual dimorphism of the CALB-ir cell cluster in the CALB-SDN strongly correlates with the gonadal sex phenotype rather than with the chromosomal sex in the Y POS mice, suggesting the effect of testicular secretion on the brain sexual differentiation with aberrant Y-linked gene expression.