Impact of Fetal Growth Restriction on the Neonatal Microglial Proteome in the Rat

Microglial activation is a key modulator of brain vulnerability in response to intra-uterine growth restriction (IUGR). However, the consequences of IUGR on microglial development and the microglial proteome are still unknown. We used a model of IUGR induced by a gestational low-protein diet (LPD) in rats. Microglia, isolated from control and growth-restricted animals at P1 and P4, showed significant changes in the proteome between the two groups. The expression of protein sets associated with fetal growth, inflammation, and the immune response were significantly enriched in LPD microglia at P1 and P4. Interestingly, upregulation of protein sets associated with the oxidative stress response and reactive oxygen species production was observed at P4 but not P1. During development, inflammation-associated proteins were upregulated between P1 and P4 in both control and LPD microglia. By contrast, proteins associated with DNA repair and senescence pathways were upregulated in only LPD microglia. Similarly, protein sets involved in protein retrograde transport were significantly downregulated in only LPD microglia. Overall, these data demonstrate significant and multiple effects of LPD-induced IUGR on the developmental program of microglial cells, leading to an abnormal proteome within the first postnatal days.