PSVI-10 - Effects of poor maternal nutrition during gestation on offspring basal immune status

Abstract: Poor maternal nutrition during gestation affects offspring pre- and post-natal growth, decreasing muscularity and increasing adiposity. Chronic inflammation may be a potential mechanism for the alterations reported. The objective of this research was to determine the effects of poor maternal nutrition during gestation on offspring inflammatory status. We hypothesized that offspring of restricted- and over-fed ewes would have an altered inflammatory status which would be dependent on offspring sex. To test this hypothesis, multiparous Dorset ewes (n=45) pregnant with twins were fed 100% (CON), 60% (RES), or 140% (OVER) of National Research Council requirements from d 30 of gestation until parturition. At parturition, all ewes were fed a control diet, such that the nutritional insult only occurred during gestation. At d 120, whole blood was collected from offspring and RNA was isolated to evaluate 86 genes related to the innate and adaptive immune responses. Data were analyzed in SAS 9.4 using PROC MIXED with fixed effects of offspring sex, maternal diet, and the interaction. Maternal diet affected 7 genes. Bovine major histocompatibility complex, a gene in the innate immune response, was downregulated by 27% and 37% in OVER compared with CON and RES, respectively (P = 0.001). Cluster of differentiation 86, a marker of T cell activation, was upregulated by 17% in OVER compared with CON (P = 0.04). Lymphocyte antigen 96, critical in the response to pathogens, expression was 48% greater in RES compared with CON (P = 0.04). A transcription factor in cytokine signaling, Signal transducer and activator of transcription 3 was upregulated in OVER and RES offspring by 19 and 21%, respectively, compared with CON (P = 0.02). Pattern recognition receptors Toll-like receptor-1 (TLR1), TLR4, and TLR8 were upregulated in RES and OVER compared with CON (P ≤ 0.04). The interaction of offspring sex and maternal diet significantly altered gene expression in 2 genes. A regulator of T cell differentiation, GATA Binding Protein 3 was downregulated in OVER females by 21 to 43% compared with all other offspring and was upregulated in OVER males by 26 to 76% compared with all female offspring (P = 0.04). A gene related to cytokine signaling, Janus Kinase 2 was upregulated in RES and OVER males by 29 to 64% compared with all other offspring (P = 0.05). Sex altered gene expression of 54 genes (P ≤ 0.05). Overall, maternal diet altered gene expression of the innate and adaptive immune responses in a sex-specific manner. Alterations in inflammatory status may contribute to altered body composition and may predispose offspring to impaired response to immune challenges. Future work should focus on the impacts of poor maternal nutrition during gestation on the response to an immune challenge.