Scientists in New York are delving into the deepest origins of male infertility in hopes of better understanding the underlying causes. They're doing this using a group of mice with a form of dysfunctional sperm similar to what might be found in a man with infertility.
The group's findings are published in this month's issue of the journal Developmental Cell.1
Male Infertility Stats
According to experts, male infertility accounts for up to 40% of infertility cases.2 Doctors evaluate possible causes of male infertility through a semen analysis, which can tell a physician about a patient's sperm count and quality.2
In addition, statistics show that more than one-half of male infertility can be corrected.3
Basis for Improved Therapies
Understanding the molecular origins of sperm abnormalities may not mean much to people with infertility now, but it's an initial step in the process leading to improved infertility treatment approaches, explain the researchers. "The sperm from these mice have problems similar to many defects seen in human sperm that contribute to infertility," said Hermann Steller, PhD, head of the Strang Laboratory of Apoptosis and Cancer Biology at Rockefeller University in New York City, and one of the study's investigators. "We have found an event in the maturation of sperm that is extremely sensitive, and thus would be a good target for both improving fertility and quality of sperm for men who are infertile …"
Led by Holger Kissel, PhD, a postdoctoral researcher in Steller's laboratory, the scientists created mice missing a gene known as Septin 4; male mice without this gene are sterile. While the rodents produce the same volume and number of sperm as normal mice, the sperm from the mutant animals are unable to fertilize eggs. They have several defects, including severely bent tails, among other things. In fact, this abnormal appearance is similar to a condition in men known as "droplet sperm".
In this condition, "the majority of sperm that even a fertile man makes appears abnormal," Kissel explained. "The sperm defects we are seeing in the mutant mice are probably an enhanced phenomenon that occurs in normal, healthy mice, as well."
A Necessary Gene for Normal Sperm
The findings come on the heels of previous research in Steller's lab4 that found that so-called "death enzymes" are a necessary part of the process of sperm production. These unique enzymes give sperm their normal, streamlined shape. The enzymes can't be activated unless the Septin 4 gene is present, Steller and his fellow investigators found. The death enzymes "are needed … to make mature sperm," Steller said.
Septin 4 is also a precursor to the construction of large scaffolds in sperm cells, similar to a construction scaffold, where different proteins assemble and house themselves in certain compartments. In this latest study, Kissel's group found that the mice lacking Septin 4 had sperm without this necessary cellular scaffolding. "…Messing that up leads to a number of problems with the sperm, including bent tails and an inability to swim," Steller said.
Findings from this study "will advance our understanding of how sperm become cells capable of fertilization," said co-investigator Gary Hunnicutt, PhD, a senior collaborative scientist at the Population Council, an international non-profit organization that conducts biomedical, social science and public health research.. This type of research will pave the way toward improving the quality of sperm in infertile men, Kissel and his colleagues maintained.
Laying the Groundwork for Future Research
"This is a really great starting point," adding Steller. "The mouse has opened up many other nice opportunities—including insights into human sterility—that we are currently pursuing."
1. Kissel H, Georgescu MM, Larisch S, Manova K, Hunnicutt GR, Steller H. The Sept4 septin locus is required for sperm terminal differentiation in mice. Dev Cell 2005 Mar;8(3):353-64.
2. American Academy of Family Physicians. Male Infertility. Available at: http://familydoctor.org/766.xml. Accessed March 22, 2005.
3. American Society for Reproductive Medicine (ASRM). Diagnostic Testing for Male Factor Infertility. Available at: http://www.asrm.org/Patients/FactSheets/Testing_Male-Fact.pdf. Accessed March 22, 2005.
4. Arama E, Agapite J, Steller H. Caspase activity and a specific cytochrome C are required for sperm differentiation in Drosophila. Dev Cell 2003 May;4(5):687-97.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
