Bone Abstracts

Experimental studies in animals indicate that particular maternal exposures during pregnancy can have specific effects on body composition in the offspring, with long-term implications for subsequent metabolic phenotype and cardiovascular risk. In animals the environment during early life induces altered phenotypes in ways which are influenced or mediated by epigenetic mechanisms, but until recently there has been little direct evidence in humans and understanding of which developmental influences can alter body composition in the offspring is incomplete. To define maternal exposures associated with offspring adiposity and elucidate underlying epigenetic mechanisms we have undertaken follow-up studies within the Southampton Women’s Survey (SWS), in which the pre-pregnant characteristics of a large group of women were assessed at recruitment; 3160 of these women have subsequently become pregnant. Body composition by dual energy X-ray absorptiometry is assessed in samples of the offspring at birth, and at 4, 6, and 8 years; we have shown greater adiposity in the offspring is associated with higher maternal adiposity, poor quality maternal diets in pregnancy, low maternal vitamin D status, excess gestational weight gain, and short duration of breastfeeding. Using Sequenom MassARRAY we have found that greater methylation of a single CpG within the RXRA promoter measured in umbilical cord was strongly associated with greater adiposity in later childhood.¹ Perinatal measurements of DNA methylation explained >25% of the variance in childhood adiposity. Findings were replicated in a second independent cohort and preliminary data link perinatal epigenetic marks with the child’s bone mineral accrual. Our data provide the first human evidence that epigenetic processes in non-imprinted genes have an important role in early growth and later body composition. Understanding the associations with maternal exposures and direct measures of adiposity provides insights into the aetiology of childhood body composition, with implications for the design of intervention studies.

Reference: 1. Godfrey KM, et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 60 1528–1534, 2011.