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

Abstract

Exposure to inflammation in utero or in early life is known 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 risk for neuropsychiatric conditions. There is some evidence that males are more susceptible to early life inflammatory challenges compared to females. In this review, we discuss the various sources of in utero or early life inflammation, and the known effects on fetal development. We also discuss these changes with a focus on sex differences in the brain, leveraging neuroimaging, as well as behavioral, cellular, and neurochemical findings. Gaining clarity on how the intrauterine environment affects offspring development is of critical importance for informing preventative and early intervention measures that may buffer against the effects of these early life risk factors.