Published Dec. 13, 2016
Proceedings of the National Academy of Sciences

Reproductive scientists have identified one more important step in the complex dance of biological activity that drives successful blastocyst implantation during the early stages of pregnancy.

Scientists have known for years that competent blastocysts must find their way to properly formed crypts in the uterine wall before further development can occur.

Now a multi-center research team provides evidence that planar cell polarity (PCP) signaling acts as a conductor in this process. This study reinforces the long-held hypothesis by the Dey Lab that disturbances during implantation create adverse ripple effects throughout the course of pregnancy.

In mouse models, the team found that PCP signaling directs epithelial evaginations to form crypts. Disrupting PCP signaling through uterine-specific deletion of Vang-like protein 2 (Vangl2)—but not Vang-like protein 1 (Vangl1)—results in defective crypt formation, embryo degeneration, and sharp reductions in litter size.

Jia Yuan, PhD, a postdoctoral fellow, and Sudhansu K. Dey, PhD, director, Division of Reproductive Sciences, led the study. Research partners included scientists from Harvard, the University of California Davis, Aix-Marseille University in France, and the National Cancer Institute.

“This study reveals a previously unrecognized role for PCP in executing spatial cues for crypt formation and implantation,” the authors state. “The knowledge derived from this study in mice will encourage basic scientists and clinical investigators to probe for PCP signaling in implantation events in humans and other species.”

While PCP signaling is an evolutionarily conserved phenomenon, it remains unclear what roles PCP signaling specifically play in human embryonic implantation.

“This signaling is particularly relevant to investigations of abnormal implantation in multiple-gestation pregnancies in humans and in placenta previa, a source of significant mortality and morbidity," Dey says.