Human Reproduction, Vol. 19, No. 3, 628-638,
March 2004
© 2004 European Society of Human Reproduction and Embryology
Increased levels of sperm ubiquitin correlate with semen quality in men from an andrology laboratory clinic population
1 Departments of Animal Science and 2 Obstetrics & Gynecology, University of Missouri–Columbia, Columbia, MO 65211-5300, 3 Department of Environmental Health, Occupational Health Program, Harvard School of Public Health, Boston, MA 02115 and 4 Vincent Memorial Obstetrics & Gynecology Service, Andrology Laboratory and In Vitro Fertilization Unit, Massachusetts General Hospital, Boston, MA 02114, USA
5 To whom correspondence should be addressed at: University of Missouri–Columbia, S141 ASRC, 920 East Campus Drive, Columbia, MO 65211-5300, USA. e-mail: SutovskyP{at}missouri.edu
BACKGROUND: Ubiquitin, a house-keeping protein that marks other proteins for proteasomal degradation, tags defective sperm during epididymal passage. To establish ubiquitin as a biomarker of human infertility, the present study examines the relationships between sperm ubiquitin content and clinical semen parameters among men from an infertility clinic population with varied aetiologies. METHODS: Anti-ubiquitin immunoreactivity was measured by flow cytometric sperm-ubiquitin tag immunoassay (SUTI) in sperm samples of 28 infertility patients and 15 fertile donors. Semen analyses were performed by computer-assisted semen analysis and World Health Organization morphology. RESULTS: Median values of ubiquitin-induced fluorescence had a strong negative correlation with sperm count (r = –0.63, P = 0.0003) and a positive correlation with % abnormal morphology (r = 0.55, P = 0.01). Infertility patients (n = 28) had significantly higher levels of sperm ubiquitin. Out of 28 patients, six reported possible occupational exposures to solvents, three were current smokers and six were ex-smokers. Within the patient group, men with known male factor infertility, those with self-reported occupational exposure to solvents and current smokers had the highest sperm ubiquitin levels. When men with jobs involving potential occupational exposure to solvents were combined with current smokers, the highest correlations were found between sperm ubiquitin and motility (r = –0.74), count (r = –0.82) and % sperm abnormalities (r = 0.73). CONCLUSIONS: Increased sperm ubiquitin was inversely associated with sperm count, motility and % normal morphology, supporting the use of ubiquitin as a biomarker of human semen quality. SUTI assay confirmed poor semen quality in all men with poor clinical semen parameters, but also was high in some patients with seemingly good clinical semen parameters. Occupational exposure to solvents and smoking may have contributed to high levels of sperm ubiquitin in some of these patients.
Key words: male infertility/sperm/SUTI assay/toxicology/ubiquitin
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