Ubiquitin-based semen quality assay in toxicology.
NIOSH 2003 Oct; :1-16
Ubiquitin is the omnipresent, house-keeping protein that binds to other proteins to mediate their degradation and recycling in both normal and diseased cells. PI's recent work implicated ubiquitin system in the control of human and animal spermatogenesis and fertilization. As the number of couples seeking treatment for male, female and unexplained infertility increases rapidly, so does the need for an objective, universal sperm quality assay. Sperm-Ubiquitin Tag Immunoassay (SUTI) has been proposed by PI as an objective diagnostic tool for male infertility diagnostics and toxicological occupational evaluation of male reproductive health. This novel experimental approach based on the objective measurement of ubiquitin levels in sperm samples, however, needed to be validated by research deciphering the various functions of ubiquitin system in male reproductive system. At the same time, it had to be determined whether the levels of sperm ubiquitin in laboratory animals commonly used in toxicological trials mirror those seen in subfertile human sperm samples. Therefore, Aims #1 and #2 of the present project sought to answer the following questions: Aim #1. Is the detection of sperm-surface ubiquitination a universal approach for assessing semen quality in men? Aim #2.. Is the rhesus monkey the optimal model for assessing the effects of workplace chemicals on male fertility and semen quality? Studies performed during two years of this project conclude that there is a strong negative correlation between sperm ubiquitin levels and male fertility/semen quality parameters in both humans and animals. Male patients with self-reported histories of occupational exposure to toxic agents, as well as male rodents exposed to known workplace toxicants have semen samples with increased levels of sperm ubiquitin. Overall protein makeup and content of ubiquitinated proteins, as revealed by proteomic analysis of sperm samples, differs between infertile men and fertile donors. Several know sperm surface proteins appear to be ubiquitinated in the defective spermatozoa. Pending the final data analysis, it is conceivable that the reproductive system of male rhesus monkeys is more sensitive to solvents than that of rodents. The benefits of this research are numerous: Deciphering the ubiquitin-dependent events during spermatogenesis can improve reproductive health of the US population at many levels, including more accurate diagnosis and treatment of male and unexplained infertility, toxicological screening, amelioration of assisted reproductive technologies (ART) and possible prevention of developmental abnormalities after ART.
Proteins; Cell-function; Diseases; Fertility; Spermatogenesis; Reproductive-system-disorders; Reproductive-system; Animal-studies; Animals; Laboratory-animals
University of Missouri - Columbia, S141 ASRC, 920 East Campus Drive, Columbia, MO 65211-5300
Final Grant Report
National Institute for Occupational Safety and Health
University of Missouri, Columbia, Missouri