Environmental Factor, October 2006, National Institute of Environmental Health Sciences
Martin Matzuk Delivers First Distinguished Lecture
By Eddy Ball
On September 12, noted clinical pathologist and reproductive biologist Martin Matzuk opened the NIEHS 2006-07 Distinguished Lecture Series with a presentation on "Genetic Dissection of Fertility Pathways" in the Rodbell Conference Center. Matzuk, the Stuart A. Wallace Chair and Professor of Pathology, Molecular and Cellular Biology, and Molecular and Human Genetics at Baylor College of Medicine, spoke to a near-capacity audience of NIEHS and area scientists and scholars. His lecture surveyed his laboratory's recent research to understand the molecular mechanisms of mammalian reproduction.
In the course of his research, Matzuk has been intrigued by the fact that 25 percent of human male infertility cases have no known cause. He speculated that these men may carry as-yet unidentified genetic anomalies in some testis-specific genes. By tracing the gene-specific fertility pathways, researchers may be able to discover clinically useful interventions. Research into mammalian reproduction may also lead to novel approaches for developing more effective means of contraception.
Matzuk's research parallels that of NIEHS researchers. The male testis is a unique organ, because it expresses genes that function in male reproduction, but are expressed nowhere else in the body. By use of genetically-engineered mouse lines Matzuk's laboratory has deleted certain of these genes and asked about their effects on different aspects of reproduction.
Matzuk's talk focused on the work he and his colleagues have performed on knockout mice using four testes-specific genes that affect male fertility. Mice deficient in one of the genes produced sperm that were less able to bind to eggs. Mice with anomalies in another gene produced sperm that were less able to traverse the female reproductive tract. These mice also showed a marked decline in fertility with age. Knockout mice with anomalies in another gene developed significantly smaller testicles than their wild type counterparts. Mice with only one copy of a normally two-copy gene showed a severe deficiency in the number of spermatozoa in their semen, leading to a high rate of male infertility.
At the end of the lecture, Matzuk turned to the direct applications of his experimental laboratory work to understanding human infertility. His clinical studies are extensive, involving collaborations with both basic scientists and physicians in a network at Baylor, universities around the country and in England. Following his talk, he joined NIEHS students and postdoctoral fellows for lunch and further discussions of fertility research.
Matzuk has contributed more than 200 scientific articles. His research focuses on the critical proteins involved in normal and abnormal reproductive development. Since 1995 he has been Co-director of Baylor's Medical Scientist Training Program, and he serves on many national and international advisory boards and review panels.