Genes deficiency tied to male mice infertility

St. Jude Children's Research Hospital (ALSAC)
Tuesday, 1 May 2001

Could open doors in understanding human male-only fertility

(Memphis, Tennessee, May 1, 2001) Male mice lacking two genes important for the control of the cell cycle will be infertile, a study published today shows. Females are not affected by this genetic deficiency.

The study may help scientists understand some forms of male-only infertility in humans.

The research, published in Molecular and Cellular Biology by scientists at St. Jude Children's Research Hospital, shows that male mice lacking the Ink4c and Ink4d genes will generate low sperm counts with reduced motility and decreased viability. These genes (named cyclin-dependent kinase inhibitors) regulate both mitotic and meiotic divisions that characterize spermatogenesis. They reside in the testis and influence the early stages of sperm production in male mice. They instruct early germ cells (spermatogonia) to become mature spermatozoa or sperm.

St. Jude's Martine F. Roussel, Ph.D., Department of Tumor Cell Biology at St. Jude, authored the study.

"Our data indicates that these two genes are essential for male fertility," Roussel said. "These two proteins collaborate in regulating spermatogenesis, helping ensure mitotic exit and the normal meiotic maturation of spermatocytes."

In the absence of these two genes, the production of spermatocytes is delayed and the production of sperm occurs improperly leading to unhealthy and non-fertile spermatozoa. This delay is associated with increased frequency of cell death.

This mouse model could help researchers understand similar forms of male infertility in humans.

"Human INK4d and INK4c genes may be candidate markers for some forms of male infertility, including those caused by autosomal recessive disorders in which early meiotic arrest is a hallmark," Roussel said.

St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is supported by the American Lebanese Syrian Associated Charities® (ALSAC®). All St. Jude patients are treated regardless of their families' ability to pay. ALSAC covers all costs of treatment beyond those covered by third-party insurers and total costs for families who have no insurance.

For more information, or to contact St. Jude Children's Research Hospital (ALSAC), see their website at: www.stjude.org