Approximately 15% of couples attempting to conceive world wide are affected by male infertility. Male infertility may be caused by heritable factors such as single gene mutations or chromosomal abnormalities, such as the XXY mutation seen in Klinefelter's syndrome. Single gene defects have been associated with decreased sperm motility due to alterations in the fibrous sheath surrounding the tail. A research article published in the American Journal of Human Genetics details a study which revealed a mutation in the CATSPER1 gene that caused heritable infertility in two four-generation Iranian families. The mutation was detected through analysis of all CATSPER genes, which had been linked to infertility in male mice. Analysis of the mutations in these families revealed that a mutation in CATSPER1, located on chromosome 11, could be causally linked to infertility in males from these families. Analysis of semen samples showed lower than normal semen volume, sperm count, percentage of motile sperm and percentage of sperm with normal form.
The CATSPER1 protein is a form of voltage-gated ion channel, expressed in the plasma membrane of spermatozoa located above the fibrous sheath in the principle piece of the tail. The protein is necessary for calcium ion-mediated sperm hypermotility, necessary for fertilisation upon entrance into the female reproductive tract. It is proposed that the discovery of this genetic defect which leads to male infertility could be utilised in the development of a new male contraceptive drug. With the new knowledge that this protein is necessary for male fertility, it is thought that blocking production of this protein through a pharmacological contraceptive would prevent fertilisation. The idea of immunocontraception using this protein has also been suggested, whereby antibodies are developed to bind to the CATSPER1 protein and prevent its functioning, causing temporary infertility. Obviously, such methods of male contraception will require testing for suitability and safety, however, it may be plausible in the future.
Source: Avenarius, MR, Hildebrand, MS, Zhang, Y, Meyer, NC, Smith, LLH, Karhizi, K, Najmabahdi,H & Smirth, RJH, 2009, American Journal of Human Genetics , 84, vol.4, pp505-510.
