Neonatal estrogen induces male-like expression of astroglial markers of maturation and plasticity in the neocortex of female mice

Astroglia play a crucial role in various aspects of neurodevelopment including building, maintaining, and modulating neuronal circuits that underly complex behaviours in the neocortex. Telencephalic regions exhibit sex differences in neuronal networks that arise early in development. Astroglia express receptors for gonadal hormones responsible for the organization of sex differences, such as estrogen, placing them in a key position to modulate sex differences in the development of neuronal networks. Astroglial cells express specific proteins related to their morphology, function, and maturation. We have previously shown that P7-P14 is a key transition period for neocortical astroglial maturation and that males reach a mature phenotype earlier than females, at P7. In this study, we investigated whether administration of perinatal estradiol to female mice is sufficient to masculinize astroglial protein and gene expression related to maturation that we previously observed at P7. We found that canonical astroglial markers like glial fibrillary acidic protein and glutamine synthetase are not affected by perinatal estrogen, but markers of astroglial maturation, Vimentin, Aldh1a1, Dio2, and the number of actively dividing astroglia are masculinized by perinatal estradiol administration. These findings suggest that sex differences in neocortical astroglial maturation are at least in-part due to the role of perinatal estrogen. Given the higher prevalence of neurodevelopmental disorders in males compared to females and the involvement of astroglia in virtually all neurodevelopmental disorders, further research is needed to determine other contributions to sex differences in neocortical astroglial cells.