Presenting on "Translational Studies on the Oxytocin Receptor; Considerations for a Personalized Medicine Approach".

Sarah England, PhD, Alan A. and Edith L. Wolff Professor of Medicine, Director, Center for Reproductive Health Sciences and Vice Chair of Research at Washington University School of Medicine, will speak on April 4, 2024 at 10:00 am CT in Whitaker 218.

Abstract: Oxytocin is a potent uterotonic agent administered to nearly all birthing people during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin. Our work shows that certain genetic variants in the oxytocin receptor (OXTR) gene impair OXTR trafficking to the cell surface, leading to an attenuated response to oxytocin in uterine smooth muscle cells. We identified that pharmacological chaperones increase oxytocin response in cells expressing WT or variant OXTRs. Screening for small-molecule agonists and antagonists of the oxytocin/vasopressin receptor family identified molecules that restored both OXTR trafficking and oxytocin response in HEK293T cells transfected with OXTR variants and restored OXT response in uterine smooth muscle cells obtained from patients at the time of Cesarean section. Our work demonstrates that pharmacological chaperones or related compounds could potentially be used to enhance clinical response to oxytocin.

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