Male Reproductive Research and Testing Lab Awarded $5 Million Grant

Involving both basic and clinical scientists, studies will focus on abnormal sperm production and the application of assisted reproductive techniques (ART) to overcome these defects. Investigators will also study the molecular biology of male infertility with specific emphasis on defining the genes required for normal male reproductive function. "It has been assumed that if a sperm can fertilize an egg, then the sperm must be healthy," says Dr. Dolores Lamb, project director and director of the Laboratory for Male Reproductive Research and Testing. "But we have no scientific basis for this belief, and many offspring produced with these sperm could be carrying genetic defects.

"We do know that male infertility is most often a consequence of too few or abnormal sperm; yet the factors that contribute to this problem are unknown," Dr. Lamb explains. "As a result, relatively little effective therapy has been developed for men with impaired sperm production."

Investigators in the Laboratory for Male Reproductive Research and Testing expect that the grant will help them successfully answer fundamental questions about genetic causes of male infertility and whether intracytoplasmic sperm injection (ICSI) is safe. Genetic causes of male infertility have not yet received much attention, but Baylor researchers believe genetics could possibly provide the answers to a range of male infertility problems, from inadequate sperm production to abnormalities in testicular descent.

The grant will allow investigators to continue their efforts to understand and find a treatment for the genetic causes of male infertility. Testicular descent is one such area currently being investigated in mouse models by Dr. Alexander Agoulnik. "It's important that we know the genetic basis of congenital defects such as failure of testicular descent or cryptorchidism," Dr. Lamb says. "Cryptorchidism is an area of urologic investigation that has received little attention despite being a common anomaly. Current research indicates that several genetic components may be responsible for this common problem.

"We have a good foundation of research information which we can build upon," Dr. Lamb says. Baylor professor Dr. Colin Bishop will clone a gene required for sufficient production of sperm in the testes and adequate numbers of eggs in the ovary. In this mouse model, males are sterile due to the absence of this gene and exhibit severe oligospermia and females develop ovarian failure.

Another phase of the project will be to investigate the safety of ICSI, which is the microinjection of a single sperm into an egg to achieve fertilization. To determine the safety of this assisted reproductive technique Dr. Lamb's study will examine both the male-factor patients who undergo ICSI and their offspring in an attempt to identify any genomic abnormalities. Researchers will follow the progress of the children born to ICSI patients for two to four years.

Dr. Lamb theorizes that many of the male patients who are currently candidates for ICSI may have genetic defects leading to their sterility. She also believes that these defects may be genetically passed on to their offspring. "Reports indicate that infertile men have a ten-fold higher incidence of chromosomal abnormalities than normal fertile men," Dr. Lamb says. "Nevertheless, nature prevents the development of most embryos with chromosomal anomalies. We hope to discover that ICSI can be used safely to overcome severe male-factor infertility and that the children resulting from these pregnancies are free of congenital defects. This project will yield important information for patients planning to achieve a pregnancy through the use of this technology."

Another phase of the investigation that will provide important information for those infertile patients using assisted reproductive techniques will be the creation of a computer- based expert system that will predict a patients' fertility potential based on their clinical patient data. "This artificial intelligence program developed by Dr. Craig Niederberger has proven to be an indispensable tool for predicting many types of medical outcomes," Dr. Lamb says. "We will continue to develop this system using the data collected from our infertile patients."

The Laboratory for Male Reproductive Research and Testing has led the way in the evaluation and treatment of male reproductive disorders in the United States, drawing approximately 1,000 new patients each year. "Thirty to 50 percent of infertility problems can be partially or solely attributed to the male," says Dr. Larry Lipshultz, director of the division of male reproductive medicine and surgery and medical director of the lab. "About one-quarter of those infertile couples have no explanation for their infertility because we have no scientific understanding of the control mechanisms regulating male fertility."

"With the aid of this grant the lab is able to assemble an extremely strong group of investigators, representing a variety of departments, to address central issues in male infertility," says Dr. Edmond T. Gonzales, chairman of the Baylor urology department. Baylor's departments of urology, obstetrics and gynecology, molecular and cellular biology, and molecular human genetics, and the department of urology at the University of Illinois at The Chicago School of Medicine will be involved in the research. "Their approach, emphasizing the molecular basis for various types of male infertility, combined with investigations of the treatment of the infertile male with assisted reproductive techniques, takes advantage of the existing strengths in the division of male reproductive medicine and surgery at Baylor College of Medicine," Dr. Gonzales continues.

"Bringing these investigators together to work on one project will create a more effective focus on male infertility than would occur with these scientists working individually," Dr. Lamb says.

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©2006 Texas Medical Center

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