In Vivo Models for Male Reproductive Toxicology

Rochelle W. Tyl1

1 Center of Life Sciences and Toxicology Research Triangle Institute, Research Triangle Park, North Carolina
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 16.1
DOI:  10.1002/0471140856.tx1601s11
Online Posting Date:  May, 2002
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

In Vivo Models for Male Reproductive Toxicology (Rochelle W. Tyl, Research Triangle Institute, Research Triangle Park, North Carolina). Assessment of male reproductive function requires a specific set of evaluations of the various steps in successful mating from sperm production to copulation to fertilization to production of a viable litter. This unit outlines the measurements that are standard for determining the effects of treatment with toxicant on the reproductive capacity of male mice and rats.

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Male Reproduction
  • In Vivo Models
  • Interpretation of Results
  • Male Endpoints
  • Figures
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Bielmeier, S.R., Best, D.S., Guidici, D.L., and Narotsky, M.G. 2001. Pregnancy loss in the rat caused by bromodichloromethane. Toxicol. Sci. 59:309‐315.
   Chapin, R.E., Sloane, R.A., and Haseman, J.K. 1997. The relationships among reproductive endpoints in Swiss mice using the reproductive assessment by continuous breeding database. Fundam. Appl. Toxicol. 38:129‐142.
   Chowdury, A., Gautam, A.K., and Chatterjee, B.B. 1984. Thyroid‐testis interrelationship during development and sexual maturity. Arch. Androl. 13:233‐239.
   Dey, S.K. 1989. Embryo development and uterine interaction in the preimplantation period. Abstr. Society of Toxicology (SOT) Symposium on Early Embryo Loss as a Factor in Reproductive Failure. 28th Annual Meeting of the SOT, Atlanta, Ga.
   Ehling, V.H., Machemer, L., Buselmaier, W., Dy'cka, J., Frohberg, H., Kratochvilova, J., Lang, R., Lorke, P., Muller, D., Peh, J., Rohrborn, G., Roll, R., Schulze‐Schenlking, M., and Wiemann, H. 1978. Standard protocol for the dominant lethal test on male mice set up by the Work Group “Dominant Lethal Mutations of the Ad Hoc Committee Chemogenics”. Arch. Toxicol. 39:173‐185.
   Environmental Protection Agency (EPA). 1996. Health Effects Test Guidelines, Report No. OPPTS 870.3800, Reproduction and Fertility Effects (Public Draft, February, 1996). Office of Prevention, Pesticides and Toxic Substances (OPPTS), U.S. EPA, Washington, D.C.
   Environmental Protection Agency (EPA). 1997. 40CFR Part 799, Toxic Substances Control Act Test Guidelines; Final Rule. Section 799.9380, TSCA reproduction and fertility effects. Fed. Regist. 62:43834‐43838.
   Environmental Protection Agency (EPA). 1998a. Health Effects Testing Guidelines, Report No. OPPTS 870.3800, Reproduction and Fertility Effects (Final Guideline, August, 1998). Office of Prevention, Pesticides and Toxic Substances (OPPTS), U.S. EPA, Washington, D.C.
   Environmental Protection Agency (EPA). 1998b. Rodent Dominant Lethal Assay, 870‐5450. Office of Toxic Substances, U.S. EPA, Washington, D.C.
   European Society for Human Reproduction and Embryology (ESHRE) Andrology Special Interest Group. 1998. Guidelines on the application of CASA technology in the analysis of spermatozoa. Hum. Reprod. 13:142‐145.
   Fail, P.A., George, J.D., Sauls, H.R., Dennis, S.W., and Seely, J.C. 1989. Effect of boric acid on reproduction and fertility of rodents. Adv. Contra. Deliv. Syst. 5:323‐333.
   Fail, P.A., George, J.D., Seely, J.C., Grizzle, T.B., and Heindel, J.J. 1991. Reproductive toxicity of boric acid in Swiss (CD‐1) mice: Assessment using the continuous breeding protocol. Fund. Appl. Toxicol. 17:225‐239.
   Fail, P.A., Pearce, S.W., Anderson, S.A., and Gray, L.E. 1994. Methoxychlor alters testosterone and LH response to human chorionic gonadotropin or gonadotropin‐releasing hormone in male Long‐Evans hooded rats. Biol. Reprod.50(suppl.1):102 (abstr. no. 206).
   Food and Drug Administration (FDA). 1982. “Redbook I” Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives Used in Food, pp. 119‐122. Center for Food Safety and Applied Nutrition (CFSAN; Bureau of Foods), U.S. FDA, Washington, D.C.
   Food and Drug Administration (FDA). 1993. Draft revised: Toxicological Principles for the Safety Assessment of Direct Food Additives and Color Additives used in Food. “Redbook II” Notice. Chapter IVc8, In Utero Exposure Phase for Addition to Carcinogenicity Studies with Rodents, in published draft. Center for Food Safety and Applied Nutrition (CFSAN), U.S. FDA, Washington, D.C.
   Food and Drug Administration (FDA). 2000. “Redbook 2000” Toxicological Principles for the Safety of Food Ingredients. Center for Food Safety and Applied Nutrition, Office of Premarket Approval (CFSAN, OPA), U.S. FDA, Washington, D.C.
   Goldman, J.M., Laws, S.C., Balchak, S.K., Cooper, R.L., and Kavlock, R.L. 2000. Endocrine‐disrupting chemicals: Prepubertal exposures and effects on sexual maturation and thyroid activity in the female rat. A focus on the EDSTAC recommendations. Crit. Rev. Toxicol. 30:135‐196.
   Green, S., Zeiger, E., Palmer, K.A., Springer, J.A., and Legator, M.S. 1976. Protocols for the dominant lethal test, host‐mediated assay, and in vivo cytogenetic test used in Food and Drug Administration's review of substances in the GRAS (Generally Regarded as Safe) list. J. Toxicol. Environ. Health 1:921‐928.
   Green, S., Auletta, A., Fabricant, J., Kapp, R., Manandhar, M., Shev, C.‐J., Springer, J., and Whitfield, B. 1985. Current status of bioassays in genetic toxicology—the dominant lethal assay. A Report of the U.S. Environmental Protection Agency Gene‐Tox Program. Mutat. Res. 154:49‐67.
   Heindel, J.J., Thomford, P.J., and Mattison, D.R. 1989. Histological assessment of ovarian follicle number in mice as a screen for ovarian toxicity. In Growth Factors and the Ovary (A.N. Hirshfield, ed.) pp. 421‐426. Plenum, New York.
   Joyce, K.L., Porcelli, J., and Cooke, P.S. 1993. Neonatal goitrogen treatment increases adult testis size and sperm production in the mouse. J. Androl. 14:448‐455.
   Kaiser, L.B., Wolfe, G.W., Lanning, L., Chapin, R.E., Klinefelter, G., and Hunter, E.S. 1996. Short‐term reproductive and developmental effects of sodium bromate in S‐D rats when administered in the drinking water. Toxicologist 30:121‐122 (abstr. no. 620).
   Kaiser, L.B., Wolfe, G.W., Lanning, L., Klinefelter, G., Hunter, E.S., and Chapin, R.E. 1997. Short‐term reproductive and developmental effects of dibromoacetonitrile in the S‐D rat when administered in the drinking water. Toxicologist 36:257 (abstr. no. 496).
   Kaiser, L.B., Wolfe, G.W., Lanning, L., Klinefelter, G., Hunter, E.S., and Chapin, R.E. 1998. Short term reproductive and developmental effects of bromoacetonitrile and hexachloroacetone in the S‐D rat when administered in the drinking water. Toxicologist 42(1‐S):100‐101 (abstr. no. 1306).
   Laskey, J.W., Berman, E., and Ferrell, J.M. 1994. The use of cultured ovarian fragments to assess toxicant alterations in steroidogenesis in the Sprague‐Dawley rat. Reprod. Toxicol. 9:131‐140.
   Leblond, C.P. and Clermont, Y. 1952. Definition of the stages of the cycle of the seminiferous epithelium in the rat. Ann. N.Y. Acad. Sci. 55:548‐573.
   Meyer, O.A., Tilson, H.A., Byrd, W.C., and Riley, M.T. 1979. A method for the routine assessment of fore‐ and hindlimb grip strength of rats and mice. Neurobehav. Toxicol. 1:233‐236.
   Miller, M.G. 1998. Reproductive system, male. In Encyclopedia of Toxicology, Vol. 3 (P. Wexler, ed.) pp. 38‐49. Academic Press, New York.
   Moser, V.C., McDaniel, K.M., and Phillips, P.M. 1991. Rat strain and stock comparisons using a functional observational battery: Baseline values and effects of Amitraz. Toxicol. Appl. Pharmacol. 1:233‐236.
   Narotsky, M.G., Hamby, B.T., Mitchell, D.S., and Kavlock, R.J. 1993. Evaluation of the critical period of bromodichloromethane‐induced full‐litter resorption in F‐344 rats. Teratology 47:429 (abstr. no. P58).
   Organization for Economic Cooperation and Development (OECD). 1995. Reproduction/developmental toxicity screening test, In Guideline for Testing of Chemicals, No. 421 (adopted July 27, 1995) pp. 1‐10. OECD, Paris.
   Organization for Economic Cooperation and Development (OECD). 1996. Combined repeated dose toxicity study with the reproductive/developmental toxicity screening test, In Guideline for Testing of Chemicals, No. 422 (adopted March 22, 1996) pp. 1‐14. OECD, Paris.
   Payne, A.H. and Sha, L. 1993. Purification and primary culture of Leydig cells. In Methods in Toxicology, Vol. 3, pt. B: Female reproductive toxicology (J.J. Heindel and R.E. Chapin, eds.) pp. 197‐209. Academic Press, San Diego.
   Reel, J.R., Lawton, A.D., Wolkowski‐Tyl, R., Davis, G.W., and Lamb, J.C. IV. 1985. Evaluation of a new reproductive toxicology protocol using diethylstilbestrol (DES) as a positive control compound. J. Am. College Toxicol. 4:147‐162.
   Robb, G.W., Amann, R.P., and Killian, G.J. 1978. Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J. Reprod. Fertil. 54:103‐107.
   Russell, L.D., Ettlin, R.A., Sinha Hakim, A.P., and Clegg, E.D. 1990. Histological and Histopathological Evaluation of the Testis. Cache River Press, Clearwater, Fla.
   Salewski, E. 1964. Farbermethode zum makroskopischen nachweis von implantationsstellen am uterus der ratte. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol. 247:367.
   Seed, J., Chapin, R.E., Clegg, E.D., Dostal, L.A., Foote, R.H., Hurtt, M.E., Klinefelter, G.R., Makris, S.L., Perreault, S.D., Schrader, S., Seyler, D., Sprando, R., Treinen, K.A., Veeramacheneni, D.N., and Wise, L.D. 1996. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: A consensus report. Reprod. Toxicol. 10:237‐244.
   Sharpe, R.M., Fisher, J.S., Millar, M.M., Jobling, S., and Sumpter, J.P. 1996. Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. Environ. Health Perspect 103:1136‐1143.
   Stoker, T.E., Parks, L.G., Gray, L.E., and Cooper, R.L. 2000. Endocrine‐disrupting chemicals: Prepubertal exposures and effects on sex maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Crit. Revs. Toxicol. 30:197‐252.
   Tyl, R.W., Myers, C.B., Marr, M.C., Brine, D.R., Fail, P.A., Seely, J.C., and Van Miller, J.P. 1999. Two‐generation reproduction study with para‐tert octylphenol in rats. Regul. Toxicol. Pharmacol. 30:81‐95.
   Tyl, R.W., Myers, C.B., Marr, M.C., Thomas, B.F., Keimowitz, A.R., Brine, D.R., Veselica, M.M., Fail, P.A., Chang, T.Y., Seely, J.C., Joiner, R.L., Butala, J.H., Dimond, S.S., Shiotsuka, R.N., Stropp, G.D., and Waechter, J.M. 2002. Three‐generation reproductive toxicity study of dietary Bisphenol A (BPA) in CD (Sprague‐Dawley) Rats. Toxicol. Sci. In press.
   vom Saal, F.S., Cooke, P.S., Buchanan, D.L., Palanza, P., Thayer, K.A., Nagel, S.C., Parmigiani, S., and Welshons, W.V. 1998. A physiologically based approach to the study of bisphenol a and other estrogenic chemicals on the size of reproductive organs, daily sperm production and behavior. Toxicol. Ind. Health 14:239‐260.
   Whitsett, J.M., Noden, P.F., Cherry, J., and Lawton, A.D. 1984. Effect of transitional photoperiods on testicular development and puberty in male deer mice (Peromyscus maniculatus). J. Reprod. Fertil. 72:277‐286.
   Whitten, W.K. 1956. Modification of the oestrus cycle of the mouse by external stimuli associated with the male. J. Endocrinol. 13:399‐404.
Internet Resources
   http://ntp-server.niehs.nih.gov/
  The National Toxicology Program (NTP) has carried out several relevant short‐term developmental and reproductive toxicity studies (accessible from their search page), including: RDGT94003, RDGT94007, RDGT94009, RDGT94013, RDGT94014, RDGT94017, and RDGT96001.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library