Kevin Sinclair

The core activity in our lab concerns metabolic programming during early mammalian development, where epigenetic outcomes are determined in embryonic cells and tissues, and long-term developmental consequences assessed in offspring. We were the first to discover that developmental anomalies following mammalian embryo culture were due to errors in genomic imprinting. Similar phenomena have since been reported in human IVF pregnancies. We were also first to demonstrate that reductions in folate and vitamin B12 in the diets of intending mothers (rat and sheep) lead to epigenetic modifications to DNA methylation and adult offspring with increased body fat and blood pressure, altered immune function and insulin resistance (showcased to the NICHD Advisory Council in Washington DC in 2007). This work was undertaken as part of UO1-HD044638 (NICHD) between 2003 and 2008. Sunsequent and ongoing Research Council funded studies are investigating the genetic variants in one carbon and related metabolic pathways that could explain inter-individual and ethnic variation in epigenetic responses to peri-conceptional diet. Our lab also provided the first detailed report of cardio-metabolic and musculo-skeletal health in aged cloned (by somatic-cell nuclear transfer (SCNT)) offspring and, most recently, provided details of concordant DNA methylation in embryonic and somatic-cell lineages. Ongoing work is determining if the nature extent of (a) mtDNA heteroplasmy and (b) DNA methylation in different cell types can explain observed differences in metabolic and musculoskeletal health within and between cloned animals. Recent Research Council LINK-funding (involving several leading breeding companies) is currently seeking to improve systems for in vitro maturation of oocytes from peri-pubertal donors. The aim is to generate sexed pig and cattle embryos that have undergone both cytogenetic and genomic evaluation in order to enhance pregnancy outcomes and to generate offspring of superior genetic merit.