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Researchers focus on gene that governs egg development

By Ruth SoRelle, MPH

Aleksandar Rajkovic, MD, PhD

While humorists ponder the old saw about the chicken and the egg , researchers at Baylor College of Medicine focus on the egg, which would not exist without the master gene Nobox.

When mice lack this gene, their eggs do not develop and they are infertile, said Aleksandar Rajkovic, MD, PhD, BCM assistant professor of obstetrics and gynecology. A report of his research appears in a recent issue of the journal Science.

Their condition resembles that of women who have ovarian failure, he said. Studying these mice may provide important clues about mechanisms of ovarian failure. It may also in the future enable "genetic control of mammalian reproductive life-span and improve our ability to regulate fertility and generate mature eggs in vitro," he said.

In the Science report, Rajkovic and his colleagues describe the actions of Nobox , a homeobox gene capable of regulating others. Homeobox genes play important roles in developmental processes. For Nobox, Rajkovic and his colleagues showed that in mice, a lack of the Nobox gene resulted in the loss of activity of other genes that are active only in the oocytes or eggs.

Nobox appears to govern the activity of genes crucial to the development of follicles, which hold the immature eggs cells or oocytes. These follicles are supposed to thicken as the mouse develops. Without Nobox , the follicles do not develop and the oocytes deteriorate.

"The preparation for early embryogenesis (formation of embryos) begins with folliculogenesis (formation of follicles)," said Rajkovic. "When this gene is deleted , there is no folliculogenesis and no oocytes."

"Are there Nobox mutations in humans? Should we be looking for them?" said Rajkovic. When a woman is born with ovarian failure, could that signal a defect in genes similar to Nobox? Is this a model for premature menopause?

"The more we look, the more we will find that these genes play a role in infertility," he said.

Others who participated in the research include Drs. Stephanie A. Pangas, Daniel Ballow, Nobuhiro Suzumori and Martin M. Matzuk.

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