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New factor affects fertility

by Ruth SoRelle, MPH

JoAnne Richards, PhD, left, and graduate student Allison Falender, PhD

On a Sunday morning, graduate student Allison E. Falender went down to evaluate overcrowding in her colony of mice in the Baylor College of Medicine facilities.

What she found surprised her. Several pairs had stopped breeding, and all of them involved a male mouse who lacked a protein called TAF4b.

When she and her mentor, JoAnne S. Richards, PhD, BCM professor of molecular and cell biology, compared one of those mice to a normal animal that had the protein, they were surprised. The testes of the mutant mouse weighed just one-quarter what those of the normal mouse weighed. From there, the two embarked on research that appeared in a recent report in the journal Genes and Development.

They found that TAF4b helps regulate gene expression in the testes and apparently affects the ability of those organs to produce and maintain levels of sperm needed for fertility.

Richards and Falender, who has completed her doctoral work in Richards' lab, said that mice that lack TAF4b are fertile at first, but by eight to 11 weeks of age become infertile and lack the precursor cells for the production of sperm.

"The fact that these animals are initially fertile indicates that the testes have the capacity to produce sperm," said Richards. "That they become infertile is related to the progressive loss of maturing germ cells in the testis."

The animals lack sperm because they cannot produce the cells that are the progenitors of sperm – cells that are usually found in adult testis.

"This is the first paper to show that in the period of growth just after birth, events occur that are important in fertility," said Richards. "The proliferation of germ cells is essential for fertility."

She said further study may indicate whether the loss of TAF4b also has an effect on the fertility of human men.

That the study began with an unexpected finding during a routine evaluation of the mouse colony amuses and pleases Richards and Falender.

"That's the fun of science – the unexpected that takes you somewhere exciting," said Richards.

Others who participated in the research include Drs. Kirk C. Lo and Dolores J. Lamb, both of BCM; Richard N. Freiman of Brown University; Kenneth G. Geles and Robert Tijian of University of California, Berkeley; KeumSil Hwang and Patricia L. Morris of The Rockefeller University in New York.

Funding for this research came from the National Institutes of Health and the American Foundation for Urologic Disease.

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