Female-specific reproductive toxicites following preconception exposure to xenobiotics
There are only a few testing strategies directed specifically at female reproductive toxicity. (Generoso et al, 1971; Generoso and Cosgove, 1973; Bishop et al., 1997). There are some elegant molecular studies of female germ cell and reproductive biology (Eichenlaub-Ritter, et al., 1988; Albertini, et al., 2001; Hunt et al, 1995) but few, if any, of these investigations involve toxicological perspectives. Future research efforts in female, as well as male, reproductive toxicology would benefit greatly by enhanced integration of knowledge and methodology from molecular developmental and cell biology. In this chapter, I will review some basic reproductive biology, emphasizing differences between females and males, describe tests for female reproductive toxicology used by the National Toxicology Program (NTP) at NIEHS, summarize NTP test data and discuss some of the dogmas of germ cell mutagenesis that have recently been dispelled by these data.
KeywordsGerm Cell Male Germ Cell Reproductive Toxicity National Toxicology Program Female Germ Cell
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- Generoso, W.M., and Cosgove, G.E., 1973, Total reproductive capacity procedure in female mice. In Chemical Mutagenesis-Principles and Methods for Their Detection (A Hollaender ed) pp. 241–258. Plenum, New York.Google Scholar
- Lockhart, A.C., Bishop, J.B., Piegorsch, W.W., 1991, Issues regarding data acquisition and analysis in the dominant lethal assay. Proceedings of the Biopharmaceutical Section of the American Statistical Association, pp. 234–237.Google Scholar
- Russell, L.B., Hunsicker, P.R., Hack, A.M., Ashley, T., 2000a, Effect of the topoisomerase-II inhibitor etoposide on meiotic recombination in male mice. Mutat Res. 464:201–212.Google Scholar
- Russell, L.B., Hunsicker, P.R., Kerley, M.K., Johnson, D.K., Shelby, M.D., 2000b, Bleomycin, unlike other male-mouse mutagens, is most effective in spermatogonia, inducing primarily deletions. Mutat Res. 469:95–105.Google Scholar
- Shelby, M.D., Bishop, J.B., Hughes, L.A., Morris, R.W., Generoso, W.M., 2001, Primary spermatocytes are the main targets for induction of etoposide dominant lethals and heritable translocations in male mice. Mutat Res. (in press)Google Scholar
- Witt, K.L., Hughes, L.A., Burka, L.T., Bishop, J.B., 2002, The mouse micronucleus assay is not a predictor of the N-hydroxymethyl acrylamide induced germ cell mutagenicity seen in the mouse dominant lethal assay. Mutat Res. (in press)Google Scholar