Maternal Vitamin D Deficiency is Associated With Sex‐Dependent Alterations in Neurodevelopment‐Related Gene Expression, Particularly in the Hypothalamus

ABSTRACT

Vitamin D (VD) is essential for calcium homeostasis and bone metabolism but also for brain development and function. However, few data are available on the impact of maternal VD deficiency (VDD) on sex‐specific brain development, particularly in specific structures such as hypothalamus. This study investigated the impact of maternal VDD on early brain development, neuronal and glial differentiation, and hypothalamic gene expression in mice. Maternal VDD was associated with increased mRNA expression of markers related to neuronal differentiation and synaptogenesis in both sexes, while mRNA expression of astrocyte‐related markers remained largely unchanged. Male offspring exhibited broader transcriptomic alterations, including dysregulation of melanocortin‐pathway and synaptic signaling genes, in the hypothalamus of early postnatal and adult mice. Maternal VDD was associated with sex‐dependent changes in gene expression relevant to early brain development, with altered mRNA expression of markers involved in neuronal differentiation and synaptogenesis in both sexes. Male offspring exhibited transcriptomic changes, including altered expression of melanocortin‐pathway and synaptic signaling genes, further suggesting greater susceptibility of hypothalamic gene expression to maternal VDD. These findings indicate that maternal VDD may influence neurodevelopmental gene expression during early life, potentially contributing to later alterations in synaptic function, metabolism, and behavior.