Skip to main content
Log in

Abnormalities in the reproductive system of aged mice after neonatal estradiol exposure

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Female mice of the BALB/c strain were treated neonatally with 17 β-estradiol (E2) or sesame oil and sacrificed at 20 months of age. Neonatal treatment of mice with E2 resulted in the development of vaginal lesions, including adenosis, adenocarcinoma and squamous-cell carcinoma. While the neonatal treatment also induced squamous metaplasia in the uterine epithelium, development of uterine adenomatous hyperplasia was markedly inhibited in the estrogen-treated mice when compared to the oil-treated controls. However, neonatal exposure to E2 resulted in a high incidence of ovarian tumors and epithelial hyperplasia of the oviduct. Thus, the effects of neonatal treatment with estrogen appeared to interact with the usual effects of aging, modifying the development of pathological abnormalities in the various reproductive organs of mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Takasugi N. Cytological basis for permanent vaginal changes in mice treated neonatally with hormones. Int. Rev. Cytol. 44: 193, 1976.

    Article  PubMed  CAS  Google Scholar 

  2. Bibbo M. Transplacental effects of diethylstilbestrol. In: Grundmann E., Kirsten W.H. (Eds.), Current topics in pathology, Perinatal pathology. Springer-Verlag, Berlin, 1979, vol. 66, p. 191.

    Google Scholar 

  3. Forsberg J.-G. Developmental mechanism of estrogen-induced irreversible changes in the mouse cervicovaginal epithelium. Natl. Cancer Inst. Monogr. 51: 41, 1979.

    PubMed  Google Scholar 

  4. Herbst A.L., Scully R.E., Robboy S.J. Prenatal diethylstilbestrol exposure and human genital tract abnormalities. Natl. Cancer Inst. Monogr. 51: 25, 1979.

    PubMed  Google Scholar 

  5. Bern H.A., Herbst A.L. Developmental effects of diethylstilbestrol (DES) in pregnancy. Thieme-Stratton, New York, 1981.

    Google Scholar 

  6. Mori T., Takasugi N. Cervico-vaginal tumors in humans and laboratory animals. In: Nagasawa H., Abe K. (Eds.), Hormone related tumors. Japan Scientific Societies Press/Springer-Verlag, Tokyo/Berlin, 1981, p. 227.

    Google Scholar 

  7. Walker B.E. Uterine tumors in old female mice exposed prenatally to diethylstilbestrol. J. Natl. Cancer Inst. 70: 477, 1983.

    PubMed  CAS  Google Scholar 

  8. Maier D.B., Newbold R.R., McLachlan J.A. Prenatal diethylstilbestrol exposure alters murine uterine responses to prepubertal estrogen stimulation. Endocrinology 116: 1878, 1985.

    Article  PubMed  CAS  Google Scholar 

  9. Ostrander P.L., Mills K.T., Bern H.A. Long-term responses of the mouse uterus to neonatal diethylstilbestrol treatment and to later sex hormone exposure. J. Natl. Cancer Inst. 74: 121, 1985.

    PubMed  CAS  Google Scholar 

  10. Newbold R.R., Bullock B.C., McLachlan J.A. Exposure to diethylstilbestrol during pregnancy permanently alters the ovary and oviduct. Biol. Reprod. 28: 735, 1983.

    Article  PubMed  CAS  Google Scholar 

  11. Newbold R.R., Bullock B.C., McLachlan J.A. Progressive proliferative changes in the oviduct of mice following developmental exposure to diethylstilbestrol. Terato. Carcino. Muta. 5: 473, 1985.

    Article  CAS  Google Scholar 

  12. Mattingly R.F., Stafl A. Cancer risk in diethylstilbestrol-exposed offspring. Am. J. Obstet. Gynecol. 126: 543, 1976.

    PubMed  CAS  Google Scholar 

  13. Bibbo M., Gill W.B., Azizi F., Blough R., Fang V.S., Rosenfield R.L., Schumacher G.F.B., Sleeper K., Sonek M.G., Wied G.L. Follow-up study of male and female offspring of DES-exposed mothers. Obstet. Gynecol. 49: 1, 1977.

    PubMed  CAS  Google Scholar 

  14. Forsberg J.-G. Late effects in the vaginal and cervical epithelia after injections of diethylstilbestrol into neonatal mice. Am. J. Obstet. Gynecol. 121: 101, 1975.

    PubMed  CAS  Google Scholar 

  15. Yasuda Y., Kihara T., Nishimura H. Transplacental effect of ethinyl estradiol on mouse vaginal epithelium. Dev. Growth Differ. 19: 241, 1977.

    Article  CAS  Google Scholar 

  16. Kalland T., Fossberg T.M., Forsberg J.-G. Localization of 3H-estradiol-17β in diethylstilbestrol-induced adenosis. Obstet. Gynecol. 51: 464, 1978.

    Article  PubMed  CAS  Google Scholar 

  17. Plapinger L., Bern H.A. Adenosis-like lesions and other cervicovaginal abnormalities in mice treated perinatally with estrogen. J. Natl. Cancer Inst. 63: 507, 1979.

    PubMed  CAS  Google Scholar 

  18. Kawashima S., Mori T., Kimura T., Arai Y., Nishizuka Y. Effects of estrogen treatment on persistent hyperplastic lesions of the vagina in neonatally estrogenized mice. Endocrinol. Jpn. 27: 533, 1980.

    Article  PubMed  CAS  Google Scholar 

  19. McLachlan J.A., Newbold R.R., Bullock B.C. Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Res. 40: 3988, 1980.

    PubMed  CAS  Google Scholar 

  20. Walker B.E. Reproductive tract anomalies in mice after prenatal exposure to DES. Teratology 21: 313, 1980.

    Article  PubMed  CAS  Google Scholar 

  21. Forsberg J.-G. Induction of conditions leading to cancer in the genital tract by estrogen during the differentiation phase of the genital epithelium. Adv. Biosci. 13: 139, 1974.

    PubMed  CAS  Google Scholar 

  22. Kimura T., Nandi S. Nature of induced persistent vaginal cornification in mice. IV. Changes in the vaginal epithelium of old mice treated neonatally with estradiol or testosterone. J. Natl. Cancer Inst. 39: 75, 1967.

    PubMed  CAS  Google Scholar 

  23. Mori T. Changes in reproductive organs and some other glands in old C3H/Ms mice treated neonatally with low doses of estrogen. Annot. Zool. Japon. 41: 43, 1968.

    CAS  Google Scholar 

  24. Mori T. Changes in the reproductive and some other organs in old C3H/Ms mice given high dose estrogen injections during neonatal life. Annot. Zool. Japon. 41: 85, 1968.

    CAS  Google Scholar 

  25. Güttner J. Adenomyosis in mice. Z. Versuchstierkd. 22: 249, 1980.

    PubMed  Google Scholar 

  26. Mori T. Changes in alkaline phosphatase activity and mitotic rate in vaginal epithelium following estrogen injections in neonatally estrogenized mice. Annot. Zool. Japon. 40: 82, 1967.

    CAS  Google Scholar 

  27. Kaufman R.H., Binder G.L., Gray P.M., Adam E. Upper genital tract changes associated with exposure in utero to diethylstilbestrol. Am. J. Obstet. Gynecol. 128: 51, 1977.

    PubMed  CAS  Google Scholar 

  28. Kaufman R.H., Adam E., Binder G.L., Gerthoffer E. Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilbestrol. Am. J. Obstet. Gynecol. 137: 299, 1980.

    PubMed  CAS  Google Scholar 

  29. DeCherney A.H., Cholst I., Naftolin F. Structure and function of the Fallopian tubes following exposure to diethylstilbestrol (DES) during gestation. Fertil. Steril. 36: 741, 1981.

    PubMed  CAS  Google Scholar 

  30. Mori T. Age-related changes in ovarian responsiveness to gonadotropins in normal and neonatally estrogenized mice. J. Exp. Zool. 207: 451, 1979.

    Article  PubMed  CAS  Google Scholar 

  31. Dunn T.B., Green A.W. Cysts of the epididymis, cancer of the cervix, granular cell myoblastoma, and other lesions after estrogen injection in newborn mice. J. Natl. Cancer Inst. 31: 425, 1963.

    PubMed  CAS  Google Scholar 

  32. Mori T., Bern H.A., Mills K.T., Young P.N. Long-term effects of neonatal steroid exposure on mammary gland development and tumorigenesis in mice. J. Natl. Cancer Inst. 57: 1057, 1976.

    PubMed  CAS  Google Scholar 

  33. Nagasawa H., Mori T., Yanai R., Bern H.A., Mills K.T. Long-term effects of neonatal hormonal treatments on plasma prolactin levels in female BALB/cfC3H and BALB/c mice. Cancer Res. 38: 942, 1978.

    PubMed  CAS  Google Scholar 

  34. Kalland T., Forsberg J.-G., Sinha Y.N. Long-term effects of neonatal DES treatment on plasma prolactin in female mice. Endocr. Res. Commun. 7: 157, 1980.

    Article  PubMed  CAS  Google Scholar 

  35. Jones L.A., Bern H.A. Cervicovaginal and mammary gland abnormalities in BALB/cCrgl mice treated neonatally with progesterone and estrogen, alone or in combination. Cancer Res. 39: 2560, 1979.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mori, T. Abnormalities in the reproductive system of aged mice after neonatal estradiol exposure. J Endocrinol Invest 9, 397–402 (1986). https://doi.org/10.1007/BF03346950

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03346950

Key-words

Navigation