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While it is commonly hypothesized that sexual differentiation in the mammalian brain is initiated mainly by gonadal sex steroids, recent evidence has suggested that dopaminergic (DA) neurons within the rodent midbrain have sex differences independent of gonadal secretions. More recently, it has been reported that Sry (the sex-determining region of the Y chromosome) is directly involved in this difference. The possibility of sexual dimorphism in the mouse midbrain needs to be elucidated. In the present study, the midbrain of C3H mice, which is little understood, was investigated histologically and immuno-histoplanimetrically to reveal sexual and developmental differences. The female ventral tegmental area appeared to contain higher immunoreactivity to tyrosine hydroxylase (TH) than that of males at 11 weeks of age, whereas general histological differences between the sexes were not clearly found. The TH-immunoreactive (TH-ir) neurons within the A8, A9, and A10 mesencephalic areas were examined separately. There was the sex difference in the time period when TH-ir cell numbers significantly increased, indicating that the growth rate of midbrain DA nuclei also differs and that the midbrain DA system may trace different processes of sexual maturation between the sexes. These differences between female and male may reflect the direct regulation by Sry or the multiple effects of both Sry and sex steroids. Further experiments are needed to determine which factor forms this difference in the growth pattern in the numbers of TH-ir neurons.

Morphological Analyses of Sex Differences and Age-Related Changes in C3H Mouse Midbrain