Role of neurotrophins in pregnancy and offspring brain development

Neurotrophins are a family of functionally and structurally related proteins which play a key role in the survival, development, and function of neurons in both the central and peripheral nervous systems. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) are the family members of neurotrophins. Neurotrophins play a crucial role in influencing the development of the brain and learning and memory processes. Studies demonstrate that they also play crucial role in influencing reproductive and immune systems. Neurotrophins have been shown to influence various processes in the mother, placenta, and fetus during pregnancy. Development and maturation of feto-placental unit and the fetal growth trajectories are influenced by neurotrophins. In addition to neurotrophins, neuropeptides like neuropeptide Y also play a crucial role during various processes of pregnancy and during fetal brain development. Neurotrophins have also been shown to have a cross talk with various angiogenic factors and influence placental development. Alterations in the levels of neurotrophins and neuropeptides lead to placental pathologies resulting in various pregnancy complications like preeclampsia, intrauterine growth restriction and preterm births. Studies in animals have reported low levels of maternal micronutrients like folic acid, vitamin B₁₂ and omega-3 fatty acids influence brain neurotrophins resulting in impaired cognitive functioning in the offspring. Maternal nutrition is also known to affect the expression of neuropeptides. It is essential to understand the role of various neurotrophins across various stages of pregnancy and its relationship with neurodevelopmental outcomes in children. This will lead to early prediction of poor neurodevelopmental outcomes. The present review describes evidence describing the role of neurotrophins in determining pregnancy outcome and altered neurodevelopment in the offspring. The possible mechanism through which maternal nutrition influences neurotrophins and neuropeptides to regulate offspring brain development and function is also discussed.