Genetics and Epigenetic Perspectives on Oxytocin Use During Labour

A major cause of postpartum hemorrhage is uterine atony or ineffective contractions. Uterine contractions depend on oxytocin signaling in the myometrium, which in turn depends on expression of the oxytocin receptor (OXTR). Dr. Erikson and her team reported a genetic by epigenetic interaction whereby the relationship between DNA hydroxymethylation and OXTR gene expression depends on a common OXTR gene variant (rs53576). They provide evidence that A carriers of rs53576 with high blood-derived DNA methylation require more oxytocin administration throughout the labor and birth process including administration for labor and/or postpartum uterine atony. A carriers with higher methylation have higher odds for postpartum hemorrhage. Prior to birth, they propose that DNA methylation of OXTR is converted to DNA hydroxymethylation to increase OXTR expression. In rs53576 G/G individuals, this DNA hydroxymethylation does lead to increased OXTR expression, but in A carriers, it does not. Thus, risk conferred by the A allele of rs53576 might be due to the inability of this allele to respond to DNA hydroxymethylation and modulate gene expression.

Future studies that replicate these results would allow for identification of women at risk for postpartum hemorrhage and other birth complications using blood-derived DNA methylation measurements and genotyping.

View Dr. Erickson's presentation here. 

More resources: 
Oxytocin receptor single nucleotide polymorphism predicts atony-related postpartum hemorrhage
Oxytocin receptor DNA methylation is associated with exogenous oxytocin needs during parturition and postpartum hemorrhage
A Common OXTR Risk Variant Alters Regulation of Gene Expression by DNA Hydroxymethylation in Pregnant Human Myometrium