Fig. 1

Cerebrovascular development and corresponding circulating levels of sex hormones throughout life in mice A Schematic timeline illustrating cerebrovascular development and neurogliovascular unit cells assembly events. Cerebrovascular development in mice begins during the embryonic stage ~ E9-E10. Brain endothelial cells (BECs) start to invade the neuroectoderm in response to local gradients of factors like vascular endothelial growth factor (VEGF). This invasion initiates the formation of primitive blood vessels within the developing brain. Between E11-E14, angiogenesis involves the sprouting of new blood vessels from pre-existing ones, contributing to the expansion of the brain vascular network. Blood–brain barrier (BBB) formation occurs between E12 and E17. During this period, tight junctions seal BECs, restricting the movement of substances across the endothelial cell layer. Between E13 and E17, pericytes wrap around BECs, contributing to the cerebrovasculature structural stability, while a basement membrane arises around blood vessels, providing additional support. After birth, brain capillary networks expand and mature, with astrocyte endfeet helping to maintain BBB integrity and actively supporting the cerebrovascular system throughout life. B Schematic illustration (not to scale) of sexual differentiation and circulating sex hormone levels from embryogenesis until adulthood. Man and woman characteristics start to develop ~ E10 (gray rectangle), via progressive elevations of testosterone in male mice (blue) and estrogen in female mice (orange) embryos. After birth, levels quickly decrease, to rise again around postnatal day 2 (P2), a period referred to as mini-puberty. In both sexes, gonadal hormone levels slowly escalate until puberty, which is characterized by monthly estrogenic cycling in women until menopause while in men, testosterone peaks then slowly decline yearly throughout adulthood. Testosterone cycling in women and estrogen cycling in men were not represented for simplicity. Early sexual differentiation coincides with several steps of cerebrovascular development, raising questions regarding potential interactions underlying sexually dimorphic cerebrovascular development (gray triangles)