# Mechanisms of maternal brain changes with birth interventions

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $659,483

## Abstract

ABSTRACT: The use of birth interventions, such as induction or augmentation of labor with exogenous oxytocin
or surgical delivery via cesarean section, have risen sharply in the past 30 years. These interventions have
contributed to a decline in maternal and infant mortality, but the long-term consequences for the mother are not
well understood. High levels of exogenous oxytocin during birth dramatically downregulate the oxytocin receptor
in the uterus. The role the receptor plays in shaping oxytocin activity in the maternal brain is unknown. Emerging
research has begun to link these birth interventions to maternal mental health and specifically to postpartum
depression. Postpartum depression is prevalent in as many as 1 in 5 new mothers, yet we know little about the
underlying biology of this disorder. Several risk factors have been identified, including changes in circulating
levels of oxytocin and epigenetic modification of the oxytocin receptor gene, OXTR. The common use of
exogenous oxytocin during birth may have long-term consequences for oxytocin functioning via OXTR epigenetic
pathways and, in turn, contribute to the oxytocin system dysfunction that increases risk for postpartum
depression. We propose to explore the link between birth intervention, changes in epigenetic markers on OXTR,
and maternal behavior in the highly social prairie vole with three specific objectives: (1) to refine a new
translational animal paradigm designed to model and study selected features of human birth practices, (2) to
test the hypotheses that altered oxytocin levels at birth, whether through labor induction or cesarean section, will
influence the behavior and brain of the mother via epigenetic effects on OXTR, and (3) to gain a deeper
knowledge of mechanisms through which birth-related interventions may have lasting functional and epigenetic
consequences for the mother. We will focus on altered epigenetic regulation of OXTR given the link between the
oxytocin receptor, birth interventions, and postpartum depression. The natural pattern of OXTR DNA methylation,
hydroxymethylation, and gene transcription will be characterized across gestation and following vaginal birth to
gain insight into epigenetic mechanisms that shape the maternal brain in response to a natural, unmanipulated
birth experience. Using exogenous oxytocin administration just prior to birth to model induction of labor in women,
these same epigenetic markers will be examined in central and peripheral tissues to investigate how a birth with
higher levels of oxytocin can alter long-term OXTR functioning and maternal behavior in new mothers. Cesarean
delivery will also be used to examine behavioral and epigenetic consequences of opposing birth experiences, or
those without pulsatile release of oxytocin during labor. The proposed experiments seek to develop a more
complete animal model of maternal oxytocin system functioning following the birth experience, particularly
epigenetic control of the re...

## Key facts

- **NIH application ID:** 10129984
- **Project number:** 5R01HD098117-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** CAROL SUE CARTER PORGES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $659,483
- **Award type:** 5
- **Project period:** 2019-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129984

## Citation

> US National Institutes of Health, RePORTER application 10129984, Mechanisms of maternal brain changes with birth interventions (5R01HD098117-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10129984. Licensed CC0.

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