Birthweight, Maternal Weight Trajectories and Global DNA Methylation of LINE-1 Repetitive Elements

Low birthweight, premature birth, intrauterine growth retardation, and maternal malnutrition have been related to an increased risk of cardiovascular disease, type 2 diabetes mellitus, obesity, and neuropsychiatric disorders later in life. Conversely, high birthweight has been linked to future risk of cancer. Global DNA methylation estimated by the methylation of repetitive sequences in the genome is an indicator of susceptibility to chronic diseases. We used data and biospecimens from an epigenetic birth cohort to explore the association between trajectories of fetal and maternal weight and LINE-1 methylation in 319 mother-child dyads. Newborns with low or high birthweight had significantly lower LINE-1 methylation levels in their cord blood compared to normal weight infants after adjusting for gestational age, sex of the child, maternal age at delivery, and maternal smoking during pregnancy (p = 0.007 and p = 0.036, respectively), but the magnitude of the difference was small. Infants born prematurely also had lower LINE-1 methylation levels in cord blood compared to term infants, and this difference, though small, was statistically significant (p = 0.004). We did not find important associations between maternal prepregnancy BMI or gestational weight gain and global methylation of the cord blood or fetal placental tissue. In conclusion, we found significant differences in cord blood LINE-1 methylation among newborns with low and high birthweight as well as among prematurely born infants. Future studies may elucidate whether chromosomal instabilities or other functional consequences of these changes contribute to the increased risk of chronic diseases among individuals with these characteristics

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth