Spermatogenesis cycle is shorter than believed

San Francisco-The average combined time necessary for both human spermatogenesis and epididymal transit time is only 64 days, according to a study using a novel in vivo, noninvasive isotope labeling method.

This contrasts with currently accepted estimates of 64 days for spermatogenesis and 5.5 days for epididymal transit time based on earlier histologic and kinetic analyses, said Shai Shefi, MD, an andrology fellow working with Paul J. Turek, MD, director of the male reproductive health center in the department of urology, University of California, San Francisco, and colleagues from KineMed, Inc.

The new study also found considerable variability among men in the time it normally takes to make and ejaculate sperm.

Dr. Shefi said kinetic studies to date have been dependent on histologic analyses of cell types within radioactive biopsies, and it has been very difficult to determine which cell actually starts the spermatogenetic cycle. Those earlier studies involved radioisotopes, were invasive, and required biopsies, he said.

The San Francisco researchers hypothesized that spermatogenesis could be assessed safely and noninvasively with a combination of modern isotope methodology, combining gas chromatography and mass spectrometry.

"Our objectives were to assess whether stable isotope assay can measure the kinetics of human spermatogenesis, and to generate pilot data on the spermatogenetic kinetics," Dr. Shefi said.

The study included 11 healthy men 50 years of age or younger with mean sperm concentration of 124 million/mL and mean motility of 42%, who ingested heavy water daily for 3 weeks. Blood samples were collected after 4 weeks of heavy water intake to calculate new sperm formed and to assess compliance. Semen was obtained regularly during the 90-day study period.

The amount of label incorporated into the deoxyribose moiety of sperm DNA was quantified by mass spectrometry in each semen specimen. Percent of new cells in the ejaculate was calculated by label incorporation, a parameter that measures DNA synthesis and thus reflects cell division. Sperm production time was assessed as the lag time from isotope ingestion until labeled sperm was detected in the ejaculate.

Dr. Shefi reported that label was detected in ejaculated sperm after a mean of 64 days. The average rate of new sperm in the ejaculate was 2.5% per day, he said. Only two patients reached the peak of new sperm in ejaculate during the study. The steep curve observed to reach this peak suggests a rapid washout of old sperm in the epididymal reservoir. Post-study semen quality was unchanged in all patients.

"Using this in vivo model to measure cell turnover, the time needed to make and ejaculate sperm is 64 days in men with normal ejaculated sperm concentration," Dr. Shefi said. "This direct, kinetic assessment is much shorter than traditional estimates."

He said the simplicity, safety, and noninvasive nature of this assay should allow it to be used in clinical practice.

"This kinetic study may improve our ability to diagnose and treat male infertility-for example obstruction versus testis failure-or to assess the effectiveness of medical or surgical infertility therapy," he said.

He added that the kinetic variability seen in healthy men in this study differs from the accepted opinion that spermatogenesis is a biological constant.

The study received funding from KineMed, Inc.