Project Grant R01HD121569

The National Institute of Child Health and Human Development awarded Yale University $543,572 on August 15, 2026, under the Child Health and Human Development Extramural Research program (CFDA 93.865) to investigate the molecular mechanisms of sperm-immune recognition in the female reproductive tract.

The research addresses how resident macrophages in the female reproductive tract selectively eliminate compromised sperm while permitting viable sperm to reach the egg. The project focuses on IZUMO1, a sperm acrosomal membrane protein that serves as a natural ligand for a macrophage receptor and becomes surface-exposed only after acrosome reaction or when sperm are compromised. The research pursues three specific aims: determining high-resolution structures of the IZUMO1–macrophage receptor complex using structural biology approaches and mutagenesis studies; visualizing receptor-mediated sperm phagocytosis to capture ultrastructural details of sperm-macrophage interactions; and profiling the human antibody repertoire against IZUMO1 by isolating IZUMO1-reactive B cells from healthy women.

The award represents $543,572 in obligated funding. Performance occurs in New Haven, Connecticut, with a completion date of April 30, 2031. The assistance type is Project Grant. This research addresses a documented gap in understanding immuno-infertility, a significant contributing factor in fertility problems affecting approximately 9 percent of men and 11 percent of women in the United States.