Protein holds key to embryo implantation

A protein called Hand2 plays a critical role in implanting a fertilized egg in the uterus by inhibiting growth of the uterine lining, a new study from the University of Illinois at Urbana-Champagne has found.

Estrogen levels rise at the beginning of the menstrual cycle, stimulating growth of the uterine epithelium. When the ovary releases an egg, progesterone levels increase and suppress growth of the epithelium, allowing implantation to occur. The new study shows that Hand2 shuts down the stimulating effect of estrogen. Researchers exposed 2 groups of mice, with and without functioning genes for Hand2, to progesterone. Epithelial growth stopped in the mice with Hand2 genes but continued in the mice without the genes.

Researchers found that progesterone stimulates release of Hand2 in uterine cells beneath the surface layer of epithelial cells. The protein causes these cells to stop producing growth factors triggered by estrogen, which in turn prompts epithelial cells to stop multiplying, mature, and become receptive to embryo implantation.

The study’s findings may have implications for progesterone-like medications used to relieve menopausal symptoms, treat infertility, and prevent preterm birth. Funding for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The research was published in Science (2011;331:912-916).