Serotonin Receptor Modulators and Congenital Heart Defects – A Translational Study Using Human Heart Organoids

Lay Summary: Some medicines taken during pregnancy might unintentionally harm the developing heart of an unborn baby, leading to serious cardiac defects, such as single ventricle defects (SVDs), where one side of the heart does not form properly. Because SVDs are rare and complex, they are challenging to study in people, animal models or through traditional surveys. Our group has developed tiny human heart models called organoids (minihearts) from stem cells that mimic early human heart development between 6-10 weeks, offering a much better way to study these issues. We discovered that a common nausea drug, ondansetron (Zofran), can impair the formation of the left ventricle without affecting the rest of the heart. Since ondansetron belongs to a broader family of drugs that target serotonin (SRMs) and that are used broadly in the clinic in pregnant women, this project aims to systematically test these drugs in the minihearts to determine which ones may cause harm. This research will not only improve drug safety during pregnancy but also create a highly accurate model for studying human heart development, reduce reliance on animal studies, and ultimately help prevent life-threatening heart defects.