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Mice Reveal A Key to Infertility

Uterine cell insights could lead to new treatments

WEDNESDAY, May 4, 2005 (HealthDayNews) -- Studies in infertile female mice are helping scientists understand why women sometimes fail to conceive.

The rodents are specially bred to lack a specific receptor on womb cells, called the lysophosphatidic acid (LPA) receptor. While they produce eggs in the normal way, after fertilization these otherwise healthy embryos have trouble implanting in the receptor-deficient womb.

The finding could apply to human females, because they also have LPA receptors lying on the surface of their uterine cells. Researchers reporting in the May 4 issue of Nature say their discovery may open up new areas of fertility research and treatment.

"There are influences that are yet to be identified in helping implantation, fertility and birth," said lead researcher Dr. Jerold Chun, a professor of neuroscience at The Scripps Research Institute, in La Jolla, Calif. "We have started to look at a new signaling pathway based on fats."

"When you take away just one fat receptor, named LPA3, it produces a change in the ability of the mouse to properly implant embryos," Chun said. "That was a surprise, because this particular signaling system had not been on anyone's radar screen in terms of influencing implantation."

In their experiments with mice lacking the LPA receptor, Chun's team found the way embryos were spaced in the womb changed, so that the number of implanted embryos was reduced. Instead of normal implantation, the embryos were clustered, with many sharing the same placenta.

"These findings suggest that there might be some other strategies for improving implantation success," Chun said. However, he cautioned that right now there is no human data to support that theory.

Factors that might alter LPA in humans include autoimmune problems and genetic factors, the California researcher added.

But Chun believes the finding might explain why the majority of failed implantations occur. "Perhaps there are these as-yet-unidentified factors that influence failed implantation rates," he said.

Fertility experts had mixed reactions to the findings.

Dr. Jaime A. Grifo, director of the Division of Reproductive Endocrinology at New York University Medical Center, cautioned that findings in mice do not always translate to humans.

"This whole system is in mice, and it's not clear how operative it is in producing infertility in normal mice," Grifo said. "The next leap is, is it present in humans in the same way, and does it have the same impact?"

Grifo also said that problems of implantation make up only a small percentage of the problems in fertility. "Most of the problems are embryonic, and not implantation problems," he explained.

Another expert, Dr. Robert Taylor, chairman of obstetrics and gynecology at Emory University, commented that, if the findings prove valid, women who use painkillers such as aspirin and Celebrex may also be at heightened risk for infertility, since these drugs can inhibit the LPA pathway.

"One of the questions is 'How safe are these drugs, in terms of having an effect on implantation?'" he said. "This is another study that would make you think that there may be risk in these drugs we commonly use. Theoretically, this might impair implantation in someone who has a problem with implantation already."

Taylor also is not sure that treating this pathway to improve implantation is wise. "This study raises more concerns to me about screwing around with that pathway than trying to use it as a way to provide some kind of therapy."

A third expert who works with similar proteins found the study to be important. "It is not totally surprising that a molecule on this pathway might be involved in implantation," said Dr. Hugh Taylor, an associate professor of obstetrics and gynecology at Yale University School of Medicine.

He disagreed with Grifo that implantation problems affect only a small number of women with fertility problems. "The major hurdle is the implantation process," he said. "And for fertility treatments, it's still the black box. We don't understand it. We can stimulate lots of eggs, we can force eggs to fertilize, but we can't get them to implant."

The Yale researcher noted that problems of implantation are the reason that doctors use multiple embryos during IVF. This often results to the birth of twins or triplets that is so common in IVF, he added.

"This is the major problem with reproductive technology today," he said. "Anything we can learn about what regulates implantation is extremely important, and this finding may lead to improvements in fertility treatment."

More information

The National Women's Health Information Center can tell you more about infertility.

SOURCES: Jerold Chun, M.D., Ph.D., professor, neuroscience, The Scripps Research Institute, La Jolla, Calif.; Jaime A. Grifo, M.D., Ph.D., director, Division of Reproductive Endocrinology, New York University Medical Center, and professor, medicine, NYU School of Medicine, New York City; Robert Taylor, M.D., professor and chairman, obstetrics and gynecology, Emory University, Atlanta, Georgia; Hugh Taylor, M.D., associate professor, obstetrics and gynecology, Yale University School of Medicine, New Haven, Conn.; May 4, 2005, Nature
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