The absence of a key protein may lead to infertility. Researchers at the University of Illinois at Urbana-Champaign report that experiments involving mice -- to be detailed in the Proceedings of the National Academy of Sciences -- indicate that the transcription factor protein C/EBPb must be present in the uterus for pregnancy to occur.
The study appears online at the PNAS Web site.
Without it, they say, an embryo cannot survive in uterine tissue or attach to a mother's blood supply. Other genes also play roles, but C/EBPb is critical for implantation of an embryo, said Milan K. Bagchi, a professor of molecular and integrative physiology.
C/EBPb is scientifically known as CCAAT/Enhancer Binding Protein beta. It is regulated by the hormones estrogen and progesterone. In normal conditions, the protein, driven mostly by progesterone, is expressed rapidly and in large quantities during the critical four-day implantation period in mice, Bagchi said.
During this period, an embryo attaches to the wall of the uterus, advances into it and eventually attaches to the blood supply and forms the placenta. For a successful pregnancy to occur, stromal cells of the uterus must be transformed into decidual cells, which secrete nutrients that allow the embryo to survive until it plugs into the blood supply. C/EBPb is necessary for decidualization, the researchers discovered.
"This protein in the mouse is also in humans," Bagchi said. "We believe it plays a critical role in human pregnancy. It is expressed in the human endometrium at a time that coincides with the time of implantation. We have demonstrated very clearly in the mouse that in the absence of C/EBPb there is no decidualization. We transferred viable mouse embryos from healthy mice into mice lacking the gene, and pregnancy failed."
The project began more than four years ago. First, researchers used DNA microarrays to identify gene expression under normal and abnormal conditions during implantation. After messenger RNA profiling zeroed in on C/EBPb's activity, the researchers collaborated with Peter F. Johnson of the National Cancer Institute's Laboratory of Protein Dynamics and Signaling, who created mice that lacked the protein.