Immune Alterations in the Intrauterine Environment Shape Offspring Brain Development in a Sex-Specific Manner

Exposure to immune dysregulation in utero or in early life has been shown to increase risk for neuropsychiatric illness. The sources of inflammation can be varied, including acute exposures due to maternal infection or acute stress, or persistent exposures due to chronic stress, obesity, malnutrition, or autoimmune diseases. These exposures may cause subtle alteration in brain development, structure, and function that can become progressively magnified across the lifespan, potentially increasing the likelihood of developing a neuropsychiatric conditions. There is some evidence that males are more susceptible to early-life inflammatory challenges than females. In this review, we discuss the various sources of in utero or early-life immune alteration and the known effects on fetal development with a sexspecific lens. To do so, we leveraged neuroimaging, behavioral, cellular, and neurochemical findings. Gaining clarity about how the intrauterine environment affects offspring development is critically important for informing preventive and early intervention measures that may buffer against the effects of these early-life risk factors.