Oxytocin receptor DNA methylation is associated with exogenous oxytocin needs during parturition and postpartum hemorrhage

Abstract

Background The oxytocin receptor gene (OXTR) is regulated, in part, by DNA methylation. This mechanism has implications for uterine contractility during labor and for prevention or treatment of postpartum hemorrhage, an important contributor to global maternal morbidity and mortality. Methods We measured and compared the level of OXTR DNA methylation between matched blood and uterine myometrium to evaluate blood as an indicator of uterine methylation status using targeted pyrosequencing and sites from the Illumina EPIC Array. Next, we tested for OXTR DNA methylation differences in blood between individuals who experienced a postpartum hemorrhage arising from uterine atony and matched controls following vaginal birth. Bivariate statistical tests, generalized linear modeling and Poisson regression were used in the analyses. Results Here we show a significant positive correlation between blood and uterine DNA methylation levels at several OXTR loci. Females with higher OXTR DNA methylation in blood had required significantly more exogenous oxytocin during parturition. With higher DNA methylation, those who had oxytocin administered during labor had significantly greater relative risk for postpartum hemorrhage (IRR 2.95, 95% CI 1.53–5.71). Conclusions We provide evidence that epigenetic variability in OXTR is associated with the amount of oxytocin administered during parturition and moderates subsequent postpartum hemorrhage. Methylation can be measured using a peripheral tissue, suggesting potential use in identifying individuals susceptible to postpartum hemorrhage. Future studies are needed to quantify myometrial gene expression in connection with OXTR methylation.

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

“…OT-R protein levels in venous and arterial blood from the umbilical cord may reveal differences in bi-directional OT-R traffic in normal, preterm and postterm deliveries. In that case, OT-R protein levels and epigenetic modifications [90] may lead to therapeutic interventions with exosomes [91] prepared, ideally, with the transmembrane orientation [12] of OT-R in villous exosomes.…”

A Influência Do Uso De Ocitocina No Trabalho De Parto Na Ocorrência De Hemorragias Pós-Parto

“…A pesquisa foi realizada nas bases de dados: Biblioteca Virtual de Saúde (BVS), Sciencedirect, PubMed, Periódicos CAPES, Biomed Central e Cochrane Library. Dessa maneira, obteve-se 355 resultados na BVS, que foram filtrados por: data de publicação (2020)(2021)(2022)(2023)(2024), tipo de estudo (retirada de revisões sistemáticas) e textos completosresultando em 85 artigos, sendo 3 selecionados. Na base Science Direct foram encontrados 3805 resultados, dos quais, após os filtros: "data de 2020-2024", retirada de "mini reviews" e de "review articles", foram encontrados 577 estudos para posterior leitura dos títulos e dos resumos, sendo escolhidos 6 ao final.…”

A prolonged latent phase: An early career in oxytocin during birth

“…Over the next couple years, despite pandemic delays and challenges, with generous support from mentors, we were ultimately able to finish analyses and publish the findings of the postpartum hemorrhage case-control study. We demonstrated that not only was DNA methylation associated with greater oxytocin needs through labor and birth but that there was higher blood loss as well, but only in births where oxytocin was used in labor [ 51 ]. In a secondary study, we found that a commonly studied the single nucleotide polymorphism (rs53576) was also predictive of postpartum hemorrhage, particularly for those with less exposure to oxytocin during labor [ 52 ].…”