Consequences of Postpartum Exogenous Oxytocin on Maternal-Neonatal Oxytocinergic Signaling and Behavior - Project Summary/Abstract The administration of exogenous oxytocin (OT) to prevent postpartum hemorrhage (PPH) is a cornerstone of obstetric care. However, the impact of this practice on oxytocinergic signaling in the offspring remains poorly understood. Our preliminary studies using a translational rat model that mimics clinical OT infusion for PPH prevention (PPH-OT) indicate that maternally administered OT may be transferred to the offspring via breast milk, leading to altered oxytocin receptor (OTR) expression and reduced sociability in male offspring. This project aims to address the potential consequences of this transfer for offspring neurodevelopment, with a specific focus on sex-specific outcomes in hypothalamic OTR-OT signaling. In Aim 1, we will quantify OT transfer from mother to offspring through breast milk. Using stable isotope-labeled OT (SIL-OT) administered to postpartum rats, we will use mass spectrometry to track SIL-OT in breast milk, neonatal plasma, and brain tissue (Aim 1a), and we will map the distribution of SIL-OT within the neonatal brain using MALDI-MSI (Aim 1b). These experiments will reveal the extent and specific brain regions affected by lactational OT exposure. In Aim 2, we will assess the impact of lactational OT exposure on OTR-OT signaling in offspring, with a focus on sex-specific responses in the hypothalamus. Guided by preliminary data showing decreased hypothalamic OTR expression and reduced sociability in male offspring, we will use RNAscope in situ hybridization to analyze hypothalamic region-specific OTR expression in male and female offspring at postnatal days 7, 14, and 21 (Aim 2a). Additionally, we will examine c-Fos expression in OT neurons within the paraventricular hypothalamus (PVH) following social interaction to assess potential sex-specific disruption in hypothalamic neuronal activation (Aim 2b). Collectively, this research will fill a significant knowledge gap in our understanding of the broader consequences of PPH-OT administration. By leveraging a novel animal model and cutting-edge analytical techniques, we aim to provide insights that could inform the optimization of OT dosing after childbirth, potentially reducing unintended neonatal exposure and informing the selection of safer uterotonic alternatives. Ultimately, our goal is to enhance maternal and neonatal wellbeing by ensuring that obstetric practices are informed by a comprehensive understanding of the physiological and behavioral effects of OT during a critical period of neurodevelopment.
