Reference SummaryNewbold RR, Carcinogenesis 1998 Sep;19(9):1655-63

Title

 Increased tumors but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilbestrol.

Authors

 Newbold RR; Hanson RB; Jefferson WN; Bullock BC; Haseman J; McLachlan JA

Journal

 Carcinogenesis

Volume

 19

Issue

 9

Year

 1998

Pages

 1655-63

Abstract

 Prenatal exposure to diethylstilbestrol (DES) has been associated with the subsequent development of reproductive tract abnormalities, including poor reproductive outcome and neoplasia, in experimental animals and humans. Experimental animal studies with chemical carcinogens have raised the possibility that adverse effects of DES may be transmitted to succeeding generations. To evaluate this possibility and to determine if there is a sensitive window of developmental exposure, outbred CD-1 mice were treated with DES during three stages of development: group 1 was treated on days 9-16 of gestation (2.5, 5 or 10 microg/kg maternal body wt), the time of major organogenesis; group II was treated once on day 18 of gestation (1000 microg/kg maternal body wt) just prior to birth; group III was treated on days 1-5 of neonatal life (0.002 microg/pup/day). Female mice (F1) in each group were raised to sexual maturity and bred to control males. As previously reported, fertility of the F1 DES-exposed females was decreased in all groups. Female offspring (DES lineage or F2) from these matings were raised to maturity and housed with control males for 20 weeks. The fertility of these DES lineage female mice was not affected by DES exposure of their 'grandmothers'. DES lineage mice were killed at 17-19 and 22-24 months of age. An increased incidence of malignant reproductive tract tumors, including uterine adenocarcinoma, was seen in DES lineage mice but not in corresponding controls; the range and prevalence of tumors increased with age. Because uterine adenocarcinomas were seen in all three DES groups, all developmental exposure periods were considered susceptible to the adverse effects of DES. These data suggest that the reduced fertility observed in the DES F1 female mice was not transmitted to their descendants; however, increased susceptibility to tumor formation is apparently transmitted to subsequent generations.

Links

 J:50278 – MGI References
9771938 – National Library of Medicine/PubMed

Strain Notes

Strain Note
CD-1 These mice were purchased from Charles River.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1 Blood vessel hemangioma Ovary

3.1
CD-1 Blood vessel hemangioma
  • diethylstilbestrol (DES)
 Ovary

5.7 - 6.3
CD-1 Blood vessel hemangioma
  • diethylstilbestrol (DES)
 Uterus

2.9 - 8.3
CD-1 Clitoral gland adenocarcinoma
  • diethylstilbestrol (DES)
 Clitoral gland

2.7
CD-1 Mesodermal cell/mesoblast sarcoma
  • diethylstilbestrol (DES)
 Uterus

2.8 - 3.4
CD-1 Muscle - Smooth leiomyoma
  • diethylstilbestrol (DES)
 Ovary

4.2
CD-1 Muscle - Smooth leiomyoma
  • diethylstilbestrol (DES)
 Uterus

4.2 - 14
CD-1 Muscle - Smooth leiomyoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

2.8
CD-1 Ovary - Granulosa cell tumor
  • diethylstilbestrol (DES)
 Ovary - Granulosa cell

6.3
CD-1 Ovary cyst Ovary

41 - 70
CD-1 Ovary cyst
  • diethylstilbestrol (DES)
 Ovary

40 - 88
CD-1 Ovary cystadenoma Ovary

6.3 - 13
CD-1 Ovary cystadenoma
  • diethylstilbestrol (DES)
 Ovary

2.9 - 18
CD-1 Ovary tumor
  • diethylstilbestrol (DES)
 Ovary

2.8 - 4.2
CD-1 Ovary tumor - gonadal stromal Ovary

4.3
CD-1 Oviduct hyperplasia Oviduct

15
CD-1 Oviduct hyperplasia
  • diethylstilbestrol (DES)
 Oviduct

14 - 44
CD-1 Placenta - Decidua deciduoma Placenta - Decidua

3.1
CD-1 Placenta - Decidua deciduoma
  • diethylstilbestrol (DES)
 Placenta - Decidua

2.7 - 6.9
CD-1 Uterus - Cervix carcinoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

4.2
CD-1 Uterus - Endometrium hyperplasia
  • diethylstilbestrol (DES)
 Uterus - Endometrium

2.7 - 6.7
CD-1 Uterus - Endometrium hyperplasia - cystic Uterus - Endometrium

9.4 - 83
CD-1 Uterus - Endometrium hyperplasia - cystic
  • diethylstilbestrol (DES)
 Uterus - Endometrium

3.0 - 69
CD-1 Uterus - Endometrium polyp Uterus - Endometrium

6.3 - 17
CD-1 Uterus - Endometrium polyp
  • diethylstilbestrol (DES)
 Uterus - Endometrium

8.6 - 31
CD-1 Uterus adenocarcinoma Uterus

0 - 0.4
CD-1 Uterus adenocarcinoma
  • diethylstilbestrol (DES)
 Uterus

0 - 16
CD-1 Uterus hyperplasia - atypical
  • diethylstilbestrol (DES)
 Uterus

2.9 - 17
CD-1 Uterus hyperplasia - atypical - focal Uterus

4.3
CD-1 Uterus metaplasia - papillary
  • diethylstilbestrol (DES)
 Uterus

2.9
CD-1 Uterus metaplasia - squamous
  • diethylstilbestrol (DES)
 Uterus

4.2 - 20
CD-1 Uterus tumor Uterus

0
CD-1 Vagina adenocarcinoma
  • diethylstilbestrol (DES)
 Vagina

2.7
CD-1 Vagina carcinoma in situ
  • diethylstilbestrol (DES)
 Vagina

2.7 - 2.8
CD-1 Vagina papilloma
  • diethylstilbestrol (DES)
 Vagina

2.9
CD-1 Vagina tumor Vagina

0