Role for estradiol in female-typical brain and behavioral sexual differentiation.
Neonatal male and female mice, ages 1-5 days, were injected intracranially with either anti-alpha-fetoprotein (AFP) IgG, steroids, or various control solutions. The mice were autopsied 60-70 days later and the spleen, thymus, liver and gonads were examined by light microscopy. The antibody to AFP produced a gonadal response which was sexual specific. Histological examination of the tissue sections from female mice treated with either anti-AFP IgG or steroids revealed the presence of polyfollicular ovaries lacking in corpora lutea formation. A comparable antibody-induced specific effect on the testes could not be demonstrated; however, steroidal administration induced aspermatogenesis and delayed maturation in parallel studies. In the anti-AFP IgG-treated groups, there appeared a gross neurological lesion which was termed external hydrocephaly. The physiologic responses in the female gonad were found independent of the presence of this anatomical brain lesion, whereas those in the male gonad were found causally related. The immunological specificity of the gonadal response was demonstrated by the use of IgG devoid of anti-AFP IgG and by various IgG control solutions. Thus, exposure to anti-AFP IgG during the critical period of sexual development in the brain appears to mimic steroidal androgenization of the female mouse.