Fall 2009
Findings in Male Infertility

synapse: University of Nevada, Reno School of Medicine

Wei Yan, M.D., Ph.D.

Yan enjoys the challenge of scientific research and understanding the mechanisms of human physiology at the cellular and molecular level. Photo by Theresa Danna-Douglas.

A research team led by Wei Yan, M.D., Ph.D., has discovered insight into the reproductive workings of the male sex chromosome that may have significant implications for male infertility and contraception.

Story by Anne McMillin, APR

The discovery findings were published this spring in Nature Genetics, one of the highest-ranking journals in the field of biomedical research.

The study, led by Yan, associate professor of physiology and cell biology, indicates that the X chromosome in developing sperm cells encodes numerous tiny ribonucleic acids, called microRNAs, despite the fact that most of genes on the X chromosomes are suppressed. This implies that these small RNAs have critical roles in chromosome inactivation and sperm formation.

“The sex chromosome silencing in meiotic male germ cells is a well-known phenomenon, which has been termed meiotic sex chromosome inactivation. I was surprised when we first observed that numerous microRNAs were highly expressed in these cells,” said Yan, principal investigator for the study.

Working in collaboration with John McCarrey, Ph.D., professor of molecular biology and reproductive biology at the University of Texas, San Antonio, Yan’s research group further investigated all the known X-linked microRNAs. Their data confirm that these X chromosome-derived microRNAs indeed escape the silencing effects and manage to be expressed.

“This finding opens a new avenue towards understanding the role of these small RNA species in the control of sperm production. Worldwide, one in nine couples in their reproductive age experiences infertility. On the other hand, the number of unintended pregnancies is increasing yearly. Since these small RNAs are involved in the control of sperm formation, they can be causative factors in male infertility and can be used as non-hormonal male contraceptive targets,” said Yan.

Graduate student Rui Song and Seungil Ro, Ph.D., an assistant professor of physiology and cell biology, co-authored this paper. Other contributing authors include Jason Michaels, a fourth-year medical student, and Chanjae Park, Ph.D., a post-doctoral researcher.

A big proponent of folding a strong research element within a medical career, Yan said there are many purposes to a medical degree and encourages his student assistants to pursue research.

“If you are a pure clinical doctor, many important things may pass you by because you won’t realize the importance of patients to basic research,” he said. Yan constantly encourages his students to do lab work as a benefit to their medical careers.

Yan’s own journey to his area of expertise followed this path. Upon earning his medical degree in China, Yan explored clinical work, forensic pathology and DNA laboratory work, but was unfulfilled because of his desire to “keep looking.”

In the mid-1990s, Yan moved from his native China to Finland as a visiting researcher where he found he enjoyed the nature of laboratory work.

“There was something new all the time. When I would solve one problem, another would come along so I was always challenged,” he said.

“To truly understand human physiology, I needed to understand the mechanism at the cellular and molecular level.”

Finding his niche as a researcher led to earning his doctorate in 2000 from the University of Turku in Finland. From there he worked as a postdoctoral scholar at Baylor University in Texas where his work on the reproductive system began in earnest, specifically with spermatogenesis and egg production.

By 2004 he was ready to move on again and, while entertaining prospects from the likes of Johns Hopkins University, he found the collegiate atmosphere at the University of Nevada School of Medicine, the opportunity to start his own lab and the Reno community all to his liking.

The clinic-oriented research study environment at the School of Medicine fit with his own philosophy and combined with the strong support of department chair Kenton Sanders, Ph.D.

Yan was excited about the possibility of working in a transgenic research lab that used genetically engineered mice for translational purposes.

“Here I can make something useful in a clinical setting for both physicians and patients,” Yan said. “I’d like to work harder to improve research and teaching and look beyond for more prestigious opportunities to raise the research reputation of the School of Medicine through my work.”

In 2007 Yan and his team reported that a novel gene controls the shape of sperm during sperm production. Mutation in this gene causes deformed sperm, which is common in male infertility patients. This discovery was published in Proceedings of the National Academy of Sciences and led to National Institutes of Health funding for additional research.

Last year, Yan’s team identified two ion channels located on the sperm tail that are required to generate sufficient forces to penetrate eggs during fertilization. This finding was published in Biology of Reproduction.

Being published in Nature Genetics is just one of three major honors Yan garnered this year.

The Society for the Study of Reproduction honored him with the Young Investigator Award in July. This honor, one of four awarded annually by the society, recognizes excellence in research by scientists within 10 years of completing their highest degree.

Earlier this year, the University of Nevada, Reno honored Yan with the Regents’ Rising Researcher award at the Honor the Best ceremony at the Joe Crowley Student Union.