Hemorrhage

Dr. Elise Erickson, PhD, CNM, FACNM, is a member of the Science of Birth cluster, and a Certified Nurse Midwife and Assistant Professor in the College of Nursing, Department of Pharmacy Practice & Science, the Clinical Translational Sciences Program, and the BIO5 Institute at the University of Arizona. Her research lab, Mechanisms Underpinning Maternal Health MuMH, is broadly focused on understanding variation in the physiology governing labor and birth to improve individualization of care practices and promote healthy transitions to motherhood/parenthood. Her recent groundbreaking paper, A common OXTR Risk Variant Alters Regulation of Gene Expression by DNA Hydroxymethylation in Pregnant Human Myometrium. Reproductive Sciences, 2024. Open Access, introduces the possibility of identification of women at risk for postpartum hemorrhage through blood-derived measurements.

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