Journal of Andrology, Vol 18, Issue 2 139-150, Copyright © 1997 by The American Society of Andrology

JOURNAL ARTICLE

Discriminant analysis indicates a single sperm protein (SP22) is predictive of fertility following exposure to epididymal toxicants

G. R. Klinefelter, J. W. Laskey, J. Ferrell, J. D. Suarez and N. L. Roberts
United States Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, North Carolina 27711, USA.

In a previous study, we found that ethane dimethanesulphonate (EDS) compromised the fertilizing ability of proximal cauda epididymal sperm from the rat within 4 days of exposure, an effect that persisted in castrated, testosterone (T)-implanted animals, establishing direct action on the epididymis. This EDS-induced reduction in fertilizing ability was highly correlated with a quantitative decrease in specific sperm protein. Here we sought to determine whether the fertility of proximal cauda epididymal sperm recovered from animals exposed to a variety of male reproductive toxicants could be predicted by assessing quantitative changes in specific sperm protein(s), or whether more common endpoints (e.g., sperm motility, sperm morphology, serum and epididymal tissue T, cauda epididymal sperm reserves) also are required to predict fertility. Intact adult male rats were dosed with EDS (25 or 50 mg/kg), chloroethylmethanesulphonate (CEMS; 12.5 or 18.75 mg/kg), or epichlorohydrin (EPI; 3 or 6 mg/kg) daily for 4 days. Castrated, T-implanted rats were dosed with hydroxyflutamide (HFLUT; 12.5 or 25 mg/kg) daily for 5 days. On day 5, proximal cauda epididymal sperm were inseminated in utero into receptive, cervically stimulated adult females, and on day 9, fertility (implants/corpora lutea) was assessed. Fertility-was decreased by the higher dose of each toxicant (P < 0.05) and also by the lower dose of EPI and HFLUT. Likewise, an acidic 22 kDa sperm protein (SP22) was decreased quantitatively (P < 0.05) in silver-stained two-dimensional gels by the higher dose of each toxicant as well as by the lower dose of EPI and HFLUT. Although sperm motility and serum T were altered by specific exposures, these endpoints were not useful in predicting fertility. In contrast, SP22 was highly correlated (P < 0.0001; r2 = 0.83) with fertility. Indeed, the amount of SP22 correctly predicted 90% and 94% of the fertile (> 50% fertility) and subfertile (< 50 fertility) animals, respectively, when discriminant analysis was performed. Thus, the amount of SP22 in a cauda epididymal sperm sample may be a useful predictor of fertility in toxicant-treated animals.

This article has been cited by other articles:

				S.-S. Cha, H. I. Jung, H. Jeon, Y. J. An, I.-K. Kim, S. Yun, H. J. Ahn, K. C. Chung, S. H. Lee, P.-G. Suh, et al. Crystal Structure of Filamentous Aggregates of Human DJ-1 Formed in an Inorganic Phosphate-dependent Manner J. Biol. Chem., December 5, 2008; 283(49): 34069 - 34075. [Abstract] [Full Text] [PDF]

				A. M. Benoit, H. A. LaVoie, G. L. McCoy, and C. A. Blake Expression of Sperm Protein 22 (SP22) in the Rat Ovary During Different Reproductive States Experimental Biology and Medicine, July 1, 2007; 232(7): 910 - 920. [Abstract] [Full Text] [PDF]

				D. N. R. Veeramachaneni, J. S. Palmer, and G. R. Klinefelter Chronic Exposure to Low Levels of Dibromoacetic Acid, a Water Disinfection By-product, Adversely Affects Reproductive Function in Male Rabbits J Androl, July 1, 2007; 28(4): 565 - 577. [Abstract] [Full Text] [PDF]

				C. Rowell, D. M. Carpenter, and C. A. Lamartiniere Chemoprevention of Breast Cancer, Proteomic Discovery of Genistein Action in the Rat Mammary Gland J. Nutr., December 1, 2005; 135(12): 2953S - 2959S. [Abstract] [Full Text] [PDF]

				A. M. Benoit, G. L. McCoy, and C. A. Blake Localization of Fertility Factor SP22 to Specific Cell Types Within the Anterior Pituitary Gland Experimental Biology and Medicine, November 1, 2005; 230(10): 721 - 730. [Abstract] [Full Text] [PDF]

				G. R. Klinefelter, L. F. Strader, J. D. Suarez, N. L. Roberts, J. M. Goldman, and A. S. Murr Continuous Exposure to Dibromoacetic Acid Delays Pubertal Development and Compromises Sperm Quality in the Rat Toxicol. Sci., October 1, 2004; 81(2): 419 - 429. [Abstract] [Full Text] [PDF]

				J. A. Olzmann, K. Brown, K. D. Wilkinson, H. D. Rees, Q. Huai, H. Ke, A. I. Levey, L. Li, and L.-S. Chin Familial Parkinson's Disease-associated L166P Mutation Disrupts DJ-1 Protein Folding and Function J. Biol. Chem., February 27, 2004; 279(9): 8506 - 8515. [Abstract] [Full Text] [PDF]

				K. Honbou, N. N. Suzuki, M. Horiuchi, T. Niki, T. Taira, H. Ariga, and F. Inagaki The Crystal Structure of DJ-1, a Protein Related to Male Fertility and Parkinson's Disease J. Biol. Chem., August 15, 2003; 278(33): 31380 - 31384. [Abstract] [Full Text] [PDF]

				T. Niki, K. Takahashi-Niki, T. Taira, S. M.M. Iguchi-Ariga, and H. Ariga DJBP: A Novel DJ-1-Binding Protein, Negatively Regulates the Androgen Receptor by Recruiting Histone Deacetylase Complex, and DJ-1 Antagonizes This Inhibition by Abrogation of This Complex Mol. Cancer Res., February 1, 2003; 1(4): 247 - 261. [Abstract] [Full Text] [PDF]

				G. R. Klinefelter, L. F. Strader, J. D. Suarez, and N. L. Roberts Bromochloroacetic Acid Exerts Qualitative Effects on Rat Sperm: Implications for a Novel Biomarker Toxicol. Sci., July 1, 2002; 68(1): 164 - 173. [Abstract] [Full Text] [PDF]

				W. D. G. Kempinas,, J. D. Suarez,, N. L. Roberts,, L. Strader,, J. Ferrell,, J. M. Goldman,, and G. R. Klinefelter Rat Epididymal Sperm Quantity, Quality, and Transit Time after Guanethidine-Induced Sympathectomy Biol Reprod, October 1, 1998; 59(4): 890 - 896. [Abstract] [Full Text]

				K. Takahashi, T. Taira, T. Niki, C. Seino, S. M. M. Iguchi-Ariga, and H. Ariga DJ-1 Positively Regulates the Androgen Receptor by Impairing the Binding of PIASxalpha to the Receptor J. Biol. Chem., September 28, 2001; 276(40): 37556 - 37563. [Abstract] [Full Text] [PDF]