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Critical Protein May be Key to Fertility

A new study from the University of Illinois1 suggests that the absence of a crucial protein may be one reason why infertility occurs. The details, published online at the website of the journal Proceedings of the National Academy of Sciences, surround a protein known as CCAAT/Enhancer Binding Protein beta, or C/EBPb. The study suggests that this protein must be present in the uterus for pregnancy to occur. Without it, an embryo cannot survive or attach to the mother’s blood supply. While other genes may also contribute to pregnancy, this particular protein is critical for embryo implantation, explained Milan Bagchi, PhD, of the University of Illinois at Urbana-Champaign.

“This [protein is produced] when the uterus is ready for embryo attachment,” said Indani Bagchi, a co-investigator and professor of Veterinary Biosciences at the University of Illinois. “Its presence indicates a window for success.”

A Human Protein, Too?
Bagchi and his fellow researchers reached their conclusions after a study using mice. The protein, they reported, is regulated by the hormones estrogen and progesterone. Under normal conditions, C/EBPb—mostly under progesterone’s control—is produced rapidly and in large amounts during the critical four-day embryo implantation period in mice.

During this time, an embryo attaches to the uterine wall, advances into it, and eventually attaches to the mother’s blood supply by forming a placenta. For a successful pregnancy to take place, the uterus’ stromal cells must be transformed into decidual cells, which then produce nutrients that allow the embryo to survive. C/EBPb is necessary, the scientists point out, for this transformation process to take place.

While results found in mice can’t always be reproduced in people, Bagchi says this study’s findings are likely applicable to humans. “This protein in the mouse is also in humans,” he explained. “We believe it plays a critical role in human pregnancy.”

As in mice, it is found in people at a time that coincides with embryo implantation in the uterus, Bagchi added. “We transferred viable mouse embryos from healthy mice lacking the [protein], and the pregnancy failed.”

Pinpointing an Infertility Cause
Why might it be important to understand this protein? If scientists in a future study confirm that lacking this protein may result in infertility in women, doctors could use it to determine a specific cause for their patients’ infertility, said Indrani Bagchi. They could potentially perform tests to search for C/EBPb. If it can’t be found, that would be very telling, she said.

One challenge in in-vitro fertilization is that conditions in the uterus when embryos are transferred are not always the best, Indrani Bagchi stated. “It’s not known if the uterus is ready to accept an embryo, so often, multiple embryos are transferred in hopes that one will attach,” she says. “In future studies, confirmation of C/EBPb that correctly indicates uterine readiness for implantation in the human is likely to alleviate those shortcomings.”

The study was sponsored by the National Institutes of Health.

1. Mantena SR, Kannan A, Cheon YP et al. C/EBPb is a critical mediator of steroid hormone-regulated cell proliferation and differentiation in the uterine epithelium and stroma. Proc Natl Acad Sci  Epub: 26 Jan 2006.

John Martin is a long-time health journalist and an editor for CuraScript. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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