Journal Article

Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol

Retha R. Newbold, Rita B. Hanson, Wendy N. Jefferson, Bill C. Bullock, Joseph Haseman and John A. McLachlan

in Carcinogenesis

Volume 21, issue 7, pages 1355-1363
Published in print July 2000 | ISSN: 0143-3334
Published online July 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.7.1355
Proliferative lesions and reproductive tract tumors in male descendants of mice exposed developmentally to diethylstilbestrol

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Prenatal exposure to diethylstilbestrol (DES) is associated with reproductive tract abnormalities, subfertility and neoplasia in experimental animals and humans. Studies using experimental animals suggest that the carcinogenic effects of DES may be transmitted to succeeding generations. To further evaluate this possibility and to determine if there is a sensitive window of exposure, outbred CD-1 mice were treated with DES during three developmental stages: group 1 was treated on days 9–16 of gestation (2.5, 5 or 10 μg/kg maternal body weight) during major organogenesis; group II was treated once on day 18 of gestation (1000 μg/kg maternal body weight) just prior to birth; and group III was treated on days 1–5 of neonatal life (0.002 μg/pup/day). DES-exposed female mice (F1) were raised to maturity and bred to control males to generate DES-lineage (F2) descendants. The F2 males obtained from these matings are the subjects of this report; results in F2 females have been reported previously [Newbold et al. (1998) Carcinogenesis, 19, 1655–1663]. Reproductive performance of F2 males when bred to control females was not different from control males. However, in DES F2 males killed at 17–24 months, an increased incidence of proliferative lesions of the rete testis and tumors of the reproductive tract was observed. Since these increases were seen in all DES treatment groups, all exposure periods were considered susceptible to perturbation by DES. These data suggest that, while fertility of the DES F2 mice appeared unaltered, increased susceptibility for tumors is transmitted from the DES `grandmothers' to subsequent generations.

Keywords: DES, diethylstilbestrol; H&E, hematoxylin and eosin.

Journal Article.  6527 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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