Maternal serum from 'high-stress' pregnancies demonstrates bioactivity capable of attenuating neurite growth through a TNFα-dependent pathway in SH-SY5Y cells.

Prenatal stress is associated with deleterious neurodevelopmental consequences in affected offspring. Prenatal stress via exposure to high physiological levels of inflammation in utero may induce an inflammatory state in the fetal brain. However, inflammation is not only associated with disease-states but also can be seen in a healthy pregnancy. There is limited research examining the potential that exposure to biological mediators of stress may have on neurodevelopment. We aim to determine whether certain circulating biological markers in maternal serum influence neurite growth in partially differentiated SH-SY5Y cells as a potential mechanism impacting neurodevelopment. Blood was collected at 20-weeks' gestation as part of the SCOPE pregnancy cohort study. These factors, including pro-inflammatory cytokines, markers of tryptophan metabolism, and gut permeability that were previously analysed, were used to stratify women into low (n = 10) and high (n = 10) biological stress groups. Exposure to the serum categorised as 'high-stress' significantly reduced neurite length in comparison to serum categorised as 'low-stress', with tumour necrosis factor-α playing a substantial role in mediating this reduction. The 'high-stress' serum was subsequently found to increase the levels of phospho-Ser536-p65. Phosphorylation of p65 Ser536 has previously been shown to switch NF-κΒ from promoting neuronal growth, to inhibiting it. The reduction in neurite length seen following exposure to the 'high-stress' serum was prevented when NF-κΒ p65 was knocked down. The present study emphasises the potential negative impact that circulating factors may have on neuronal growth, and the mechanism behind it.