A newly discovered genetic abnormality that appears to prevent some men from fathering children could be the key to developing a male contraceptive, said University of Iowa researchers who reported their findings in the April 2 online edition of the American Journal of Human Genetics.
Although female oral contraceptives were developed more than 40 years ago and have proven very effective for family planning, no similar pharmacological contraceptive has been developed for males. Surveys conducted by the Medical Research Council Reproductive Biology Unit in the United Kingdom suggest that men would be willing to use a pharmacological contraceptive if one were available. Presently, the only contraceptives available for men are condoms or a vasectomy.
"We identified CATSPER1 as a gene that is involved in nonsyndromic male infertility in humans, a finding that could lead to future infertility therapies that replace the gene or the protein.
"But, perhaps even more important, this finding could have implications for male contraception," said Michael Hildebrand, PhD, co-lead author of the study and a UI postdoctoral researcher in otolaryngology at the UI Roy J. and Lucille A. Carver College of Medicine.
Gene Mutations
The research team, which included scientists from the University of Social Welfare and Rehabilitation Sciences in Tehran, Iran, discovered the male infertility gene while studying the genetics of families from Iran, where there are population groups that have relatively high rates of disease-causing gene mutations.
Although the team's research with these Iranian families focuses on identifying genetic causes of deafness, collecting genetic information from this population allowed the researchers to identify two families in which male infertility that was not part of a syndrome appeared to be inherited.
Focusing on a group of genes that have been implicated in male infertility in mice, the researchers found that mutations in both Iranian families occurred in a single gene called CATSPER1.
"Our research suggests that the defect in sperm hyperactivity seen in mice without CATSPER1 will also occur in humans with the genetic mutation," Hildebrand said. "Identification of targets such as the CATSPER1 gene that are involved in the fertility process and are specific for sperm provide new targets for a pharmacological male contraceptive."
Several approaches to male contraception are currently under investigation at other institutions. One approach that could potentially target CATSPER1 is immunocontraception, where antibodies are developed that bind to a targeted protein and block its function. Immunocontraception is still in the early stages of development, and in order to be useful, it will need to be proven effective, safe and reversible.
The UI research team was led by Richard Smith, MD, the Sterba Hearing Research Professor and vice-chair of otolaryngology. Matthew Avenarius, now a graduate student at the University of Michigan, was study co-lead author with Hildebrand. Avenarius was a research assistant in Smith's UI lab when the study was done. |
