Monday, 16 January 2006 00:00

Gene May Help Cause Infertility

MONDAY, Jan. 16 (HealthDay News) -- Scientists say dysfunction in a key gene could explain many cases of female infertility.

In studies in mice, embryos without a gene that expresses a uterine protein called CCAAT/Enhancer Binding Protein beta (C/EBPb) could not survive in uterine tissue or attach to the mother's blood supply.

"This protein in the mouse is also in humans," lead researcher Milan K. Bagchi, a professor of molecular and integrative physiology at the University of Illinois, said in a prepared statement. "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."

The report appears in this week's early online edition of the Proceedings of the National Academy of Sciences.

According to Bagchi, C/EBPb is regulated by estrogen and progesterone. Normally, it is driven mostly by progesterone, and is produced rapidly and in large quantities during the critical four-day implantation period in mice.

During this period, the embryo attaches to the uterine wall and eventually attaches to the mother's blood supply and forms the placenta. For a successful pregnancy, a process called decidualization needs to occur. Decidualization produces changes in the lining of the uterus that allow the embryo to link to the mother's blood supply. C/EBPb is necessary for decidualization, Bagchi's team found.

"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," he said.

Study co-author Indrani C. Bagchi, a professor of veterinary biosciences in the College of Veterinary Medicine at Illinois, said in a statement, "This gene is expressed when the uterus is ready for embryo attachment. Its presence indicates a window for success."

She also believes the finding could lead to more successful treatment for infertility.

"The success rate for the practice of in vitro fertilization currently is, on average, about 25 percent," she explained. "The major problem is that the conditions occurring when the embryo is transferred often are not the best in the uterus. 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. In future studies, confirmation of C/EBPb as a marker that correctly indicates uterine readiness for implantation in the human is likely to alleviate these shortcomings."

However, another expert said it is unclear whether C/EBPb will have the same function in humans as it does in mice.

"This is so far away from the human," said Dr. Richard J. Paulson, a professor of reproductive medicine at the University of Southern California.

He added that doctors already have effective methods of helping patients overcome uterine implantation difficulties. "In women who have had their ovaries removed, giving them estrogen and progesterone can induce pregnancy that is just as good as it is in women who have functioning ovaries," he pointed out.

"Through the advent of assisted reproduction, and particularly egg donation, it was discovered that estrogen and progesterone could be supplemented, and that this results in perfectly good receptivity of the uterus," Paulson said.

Paulson said the study does enhance understanding of key factors involved in pregnancy. "Its implication is uncertain in humans," he said. "We don't know if this factor is important, and in addition, we have not as yet identified a population of women who do not respond to estrogen and progesterone."

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