Biochemical Development of the Fetus/Neonate and Maternal Diet

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Since its inception, my research program has investigated the biochemical development of the fetus and neonate with the overall goal of identifying nutritional and non-nutritional determinants of perinatal growth and organ development. Four novel experimental approaches have been used. These include (1) the characterization of the nutrient composition of amniotic fluid (AF) which is continuously swallowed by the growing fetus and may provide an important first window into the early biochemical development of the fetus; (2) an exploration of novel bioactive, components in milk, including but not limited to inflammatory markers and cytokines, and their impact on postnatal growth and development; and (3) an investigation into mechanisms by which gastrointestinal nematode infections when coupled with nutritional deficiencies impair perinatal growth and organ development. During the tenure of my last NSERC grant, each approach resulted in new insights. First, evidence emerged to show that albumin, the major protein in AF, can be irreversibly oxidized, suggesting an important but underappreciated role for dietary antioxidants early in pregnancy. Secondly maternal protein deficiency and infection impaired immune development by increasing pro-inflammatory cytokines and lowering concentrations of growth factors in plasma and in milk. Thirdly protein deficiency and infection impaired fetal and neonatal growth and organ development differently and these differences were associated with important compartmental changes in concentrations of cortisol, growth factors, proinflammatory cytokines in plasma, amniotic fluid and in milk. The overarching goal of the current discovery grant is to continue to explore the biochemical determinants of perinatal growth and development with following specific aims: AIM 1: The first aim will explore how amniotic fluid nutrients and newly emerging bioactive constituents (miRNAs, EPO, cytokines and growth factors) contribute to the regulation of early fetal growth. A secondary approach is to explore if oxidative stress itself impairs fetal growth or will the presence of dietary antioxidants in AF be of some benefit? AIM 2: Mastitis, an asymptomatic breast inflammation, is associated with changes in the milk microbiome, increased milk cytokines and impaired growth. We will explore if inflammation induced changes in milk composition (nutrients/growth & immune factors, microbiome) impair neonatal growth. AIM 3: The third aim explores how inflammation and immunity, commonly associated with gastrointestinal nematode infections and maternal protein deficiency, impact perinatal organ development. A secondary objective is to determine if these changes occur through alterations in the intestinal microbiome and/or differential expression on gene transcripts in developing fetal and neonatal organ systems?