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RELATIONSHIPS AMONG SEMEN ENDPOINTS USED AS INDICATORS OF SPERM NUCLEAR INTEGRITY
Citation:
JEFFAY, S. C., L. F. STRADER, R. M. BUUS, D. P. EVENSON, A. F. OLSHAN, A. H. HERRING, L. E. BRADLEY, J. C. SMITH, AND S. P. DARNEY. RELATIONSHIPS AMONG SEMEN ENDPOINTS USED AS INDICATORS OF SPERM NUCLEAR INTEGRITY. Presented at American Society of Andrology, Chicago, IL, April 08 - 11, 2006.
Description:
Recent attention has been directed towards developing assays that measure the genomic integrity of the sperm nucleus with the objective of predicting infertility, and/or the risk of sperm-mediated miscarriage or development deficits. These assays are also being used in efforts to detect toxicant-induced DNA and or chromatin damage in semen from men exposed to environmental contaminants. In an ongoing environmental epidemiology study, we have included two of these assays, the Sperm Chromatin Structure Assay? (SCSA), and chromomycin A3 (CMA) staining along with routine semen analysis. Men enrolled in this study are residential partners of pregnant women. The resulting database provides an opportunity to examine potential correlations between these endpoints in a cohort of presumed fertile men, and to ask whether they relate to sperm concentration and sperm morphology. Semen samples from 182 men (aged 18-40) were shipped via overnight courier (with cold packs) for analysis at a central EPA laboratory. Upon arrival, 100?l aliquots were frozen and stored at -80?C until analysis by SCSA and CMA. Two outcomes of SCSA, the DNA fragmentation index (%DFI), a measure of DNA damage, and %HDS (% sperm with high green staining, an indication of incompletely condensed chromatin) were not significantly correlated (r=0.038, p=0.61), suggesting, as expected, that they measure independent features of sperm nuclei. %HDS, on the other hand, was significantly correlated with %CMA+ sperm (r=0.610, p<0.0001). CMA staining is thought to reflect under-protamination of sperm DNA, a phenomenon that could result in incomplete condensation. This correlation suggests that these two assays measure a common feature of sperm nuclei. Interestingly, %CMA+ sperm was also correlated with %DFI (r=0.276, p<0.002), though less strongly than with %HDS. As has been reported previously, %DFI correlated with neither sperm morphology nor sperm concentration. In contrast, both %HDS and %CMA+ were significantly correlated with both of these routine measures. Taken together, these observations provide insights into the interpretation of sperm nuclear integrity assays. As has been shown in infertility patients, DNA fragmentation may be present in the absence of other semen abnormalities; therefore, %DFI can be considered a relatively independent predictor of infertility or abnormal pregnancy outcomes. On the other hand, %HDS and %CMA appear to be less independent of routine semen measures such as sperm concentration and morphology. Funded by CR 829327 (AFO). This abstract does not necessarily reflect EPA policy.