HOUSTON - Illuminating the molecular details of normal sperm development, demonstrating how chemotherapy or radiation can leave a man or boy sterile, and pursuing ways to restore fertility have earned a major honor for a scientist at The University of Texas M. D. Anderson Cancer Center.
Marvin Meistrich, Ph.D., professor in M. D. Anderson's Department of Experimental Radiation Oncology, will be inducted as a fellow of the American Association for the Advancement of Science at the association's annual meeting Saturday, Feb. 14, in Chicago.
"Our goal is to find ways to restore the fertility of the thousands of young men and boys every year who receive treatment that might leave them sterile while curing their disease," Meistrich said.
AAAS, founded in 1848, is the world's largest general scientific society. Meistrich is the eighth AAAS fellow on M. D. Anderson's faculty.
"Addressing quality-of-life issues that arise from surviving cancer is an increasingly important aspect of our research. Recognition of Dr. Meistrich's leadership and innovation in this field is richly deserved," said Raymond DuBois, M.D., Ph.D., M. D. Anderson provost and executive vice president and an AAAS fellow since 2004.
Before undergoing treatment now, men can bank their sperm for later in vitro fertilization. Boys have no options for later reproduction. Chemotherapy and radiation destroy stem cells called spermatagonia that differentiate into sperm. If all the stem cells are destroyed, sterility results.
"An important focus of our research is the possibility of banking these sperm stem cells before treatment and then transplanting them later to launch normal sperm production," Meistrich said. This procedure is done now in mice, and Meistrich's plan is to attempt the same in primates.
Normal sperm production begins with the spermatagonia, which either divide into more stem cells or differentiate into cells called spermatocytes then to spermatids and finally sperm, with the male hormone testosterone crucially involved all along.
A major, surprising discovery by Meistrich and colleagues implicates testosterone in the inability of surviving stem cells to restore sperm production after radiation or chemotherapy.
"This was exactly backwards from what we expected to find," Meistrich said. Rat experiments showed that surviving stem cells could not make the next step in sperm development - differentiation into spermatocytes - because of testosterone's effects on the cells that support and nourish the developing sperm cells.
"So we suppressed testosterone until spermatocytes formed, then restored it to complete the process of sperm development," Meistrich said. While this has worked in rodents, translating it to primates has been more complicated, Meistrich said.
"We are trying to understand the molecular mechanism at work in rodents so we can manipulate that mechanism in primates," he said.
Other major contributions from Meistrich's lab include:
- Development of methods to separate the different cell types in the sequence of sperm development, or spermatogenesis.
- Demonstration that X- and Y-chromosome sperm can be distinguished from each other through flow cytometry, which led to sorting of these cells.
- Collaboration with M. D. Anderson clinical faculty to determine which chemotherapeutic and radiation treatments at what doses cause sterility. The resulting information is used in counseling patients about their reproductive options before treatment.
- Discovery that cancer therapies produce a five-fold increase in chromosome number mutations in sperm formed during treatment. These mutations, which pose a risk of spontaneous abortion or birth defects if conception occurs during or soon after therapy, return to baseline levels months after treatment. Patients are now counseled about this elevated short-term risk and informed that there is no detectable risk if conception occurs 6 months to a year after therapy.
Other M. D. Anderson fellows are Jack Roth, M.D., professor in the Department of Thoracic and Cardiovascular Surgery; Isaiah J. Fidler, D.V.M., Ph.D., professor in the Department of Cancer Biology; Waun Ki Hong, M.D. professor of head and neck medical oncology and head of M. D. Anderson's Division of Cancer Medicine; Margaret Kripke, Ph.D., professor of immunology, special advisor to the provost; Robert C. Bast Jr., M.D., vice president for translational research; Louise Strong, Ph.D., professor of cancer genetics; and Emil J. Freireich, M.D., professor in the office of the provost.
Nominations to AAAS are offered by at least three existing fellows in one of the association's 24 sections, or by the section's steering group, or by the AAAS chief executive officer. The steering groups review nominations and send a final list to the AAAS Council for a vote.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For four of the past six years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.