The new study - a collaboration between the Universite de Montreal in Canada and the Institut de genetique et biologie moleculaire et cellulaire of the Universite de Louis Pasteur, Strasbourg, France - is published in the latest issue of the journal Genes & Development.

"Our findings demonstrate that the Lrh1 gene is essential in regulating ovulation," said Bruce D. Murphy, director the Animal Research Centre at the Faculty of Veterinary Medicine and an adjunct professor of and obstetrics and gynaecology at the Faculty of Medicine of the Universite de Montreal. "Until this point, the role of Lrh1 in female fertility was unclear, but we have found the gene regulates multiple mechanisms of ovulation and may affect fertilization."

To reach their conclusions, the research team developed a new type of genetically modified mouse whose Lrh1 gene was selectively blocked in the ovary. They found that deletion of the Lrh1 gene effectively stopped ovulation. "This discovery means we can envision new contraceptives that selectively stop ovulation," said Dr. Murphy. "If created, these new contraceptives would be more effective and produce less side-effects than current steroid-based forms of birth control."

What's more, the findings could lead to the development of pharmaceuticals that activate the Lrh1 gene, which may prove critical in giving infertile couples hope in producing children. "This is an important development, since 15 percent of couples are infertile," said Dr. Murphy. "The widespread role of this gene in the ovary indicates that it may be targeted to stimulate ovulation and, eventually, conception."

umontreal

Today diagnosing PAD relies mainly on detection of abnormal pulse volumes in the lower limbs, or blood pressure differences between separate readings at the ankle and the arm (the ankle-brachial index), but these are only effective in detecting moderate-to-severe cases and do not always detect disease in the small vessels.

"The real benefit of a test like this - which only takes about five minutes to do and doesn't require anything beyond the equipment and capabilities already in place in most vascular laboratories - is their value for selecting the right therapies," said Lindner. "There are new drugs in clinical trials at OHSU and elsewhere that involve gene and stem cell therapies aimed at improving the circulation by promoting new blood vessel growth. But the symptomatic benefits you get from these therapies generally can't be evaluated by conventional tests because they don't really test tissue perfusion. If you want to look at the improvement in perfusion, why not look at perfusion?"

Further studies are needed on subjects for whom no diagnosis has yet been made. The microbubbles used in the test already are approved for human use, although the PAD test is currently an off-label application. The technique does require additional training in how to receive the microbubble signals, said Lindner, but otherwise there are few significant hurdles yet to be cleared for the test to be used in vascular clinics everywhere.

The findings of the Lindner study were detailed in a recent issue of JACC: Cardiovascular Imaging, a peer-reviewed journal of the American College of Cardiology Foundation. [J Am Coll Cardiol Img, 2008; 1:343-350, doi:10.1016/j.jcmg.2008.04.001] imaging.onlinejacc/cgi/content/abstract/1/3/343.

ohsu/