Early environments, epigenetics, and inflammation during pregnancy

Epidemiological and clinical research indicates that chronic inflammation contributes to a wide range of disease processes, but these studies are conducted primarily among affluent industrialized populations representing a very limited range of ecological variation. Recent research in biological anthropology, in diverse field-based settings, has emphasized that ecological responsiveness and developmental plasticity are important features of human immune function, including inflammation. The proposed research investigates how environments early in life, during sensitive periods of immune development, have long term effects on the regulation of inflammation in adulthood. The study focuses on pregnant women, since inflammatory pathways are activated as part of normal pregnancy, but dysregulated inflammation contributes to adverse birth outcomes. The specific objectives of the project are as follows: 1) To investigate microbial, nutritional, and psychosocial environments early in life as predictors of inflammatory markers in adulthood, during pregnancy; 2) To determine whether patterns of inflammation during pregnancy are associated with birth outcomes; 3) To investigate methylation of inflammatory genes—an epigenetic process that reduces gene expression—as a mechanism linking early environments, inflammation, and birth outcomes. Data and samples come from an ongoing cohort study in the Philippines that has followed the same individuals since their mothers were pregnant with them in 1983-84. In the first phase of the project, blood samples from N=527 pregnant women will be analyzed for IL6 and TNFα (pro-inflammatory cytokines), and IL10 (anti-inflammatory cytokine). Results will be used to test the hypothesis that microbial, nutritional, and psychosocial environments in infancy have lasting effects on the regulation of inflammation in adulthood. Measures of inflammation during pregnancy will also be evaluated as predictors of offspring birth weight and gestational age. In phase two, the methylation status of pro- and anti-inflammatory target genes will be determined. These results will be used to test the hypothesis that DNA methylation represents a mechanism of developmental plasticity through which environments in infancy are embodied, and have a lasting effect on the regulation of inflammation in adulthood, with implications for the gestational environment of the next generation. Intellectual merit of the project includes the application of a developmental, intergenerational model to investigate how environments in infancy shape inflammatory phenotypes in adulthood, with a focus on pregnancy as a key moment when early environments in one generation may reach into the next. The project advances human ecological immunology and evolutionary medicine as important areas of research within biological anthropology, and it contributes to growing interest in epigenetics as potentially important mechanisms through which early life environments have lasting phenotypic effects. Broader impacts include the promotion of international collaboration, and contributions to the infrastructure of science by providing mentored research experiences for graduate students who will be involved in all phases of the research. The project may contribute to well-being by generating knowledge that improves birth outcomes and prevents chronic diseases of aging in the US and globally, while dissemination of epigenetic findings may advance public understanding of the human genome as a dynamic substrate that incorporates information from the environment to alter