Secrets of the Crypt: Scientists Dig Deeper for Clues About Pregnancy

Published February 9, 2018 | Nature Communications

A combination of 3-D imaging and molecular testing is revealing new insight into the early stages of mammalian pregnancy, and is helping scientists unravel more of the genetic and molecular causes of infertility.

Now a study led by Sudhansu K. Dey, PhD, Director of the Division of Reproductive Sciences, and colleagues Jia Yuan, PhD, and Wenbo Deng, PhD, details a critical role played by the gene Vangl2.

The study, based on mouse models, shows that glands in the uterus must link and communicate directly with the embryo for successful implantation.

This connection occurs inside implantation chambers in the uterus called crypts, and remains in place through pregnancy’s early stages.

“The gland secretions produce molecules essential to embryo development,” Dey says. “The Vangl2 gene is critical to this process—without it, the glands do not extend and connect to the embryo, and the embryo does not properly implant.”

The study includes unprecedented visual and molecular detail about the early stages of a normal mouse pregnancy.

The team used the data to compare normal mouse pregnancy to malformations that occur in the uterus when Vangl2 is deleted from epithelial cells in the lining of uterine cells and glands.

The team also found that a growth factor protein called HB-EGF (heparin-binding EGF-like growth factor) coordinates with Vangl2 to initiate the gland extension process.

“Further research is warranted into the potential of HB-EGF as a potential therapy for recurrent pregnancy failures,” Dey says.