Skip to main content
SpringerLink
Log in
Book cover

Endocrine Disrupters pp 81–118Cite as

The ‘Des Syndrome’: A prototype of Human Teratogenesis and Tumourigenesis by Xenoestrogens?

  • Chapter

Part of the book series: Environmental Science and Technology Library ((ENST,volume 18))

Summary

Diethylstilboestrol (DES), the first synthetic hormone, when antenatally prescribed to prevent spontaneous abortion, has been described in the offspring to cause a variety of congenital abnormalities of the female genital tract. In addition, with an estimated absolute risk of 1:1000, it also causes clear cell adenocarcinoma (CCA) of the vagina and cervix in young `DES-daughters’. Also neuroteratogenic effects have been attributed to DES, but the psychopathology in DES-exposed persons is shown here to be largely iathrogenic, i.e., as a consequence of having been disproportionately alarmed by its potential toxicity. With over 20,000 publications, DES is one of the most studied compounds ever. Yet, many doubts persist on its mechanisms of action, on whether or not it may have prevented some abortions, on the epidemiology and causation of CCA, and in how far it may have affected humans through the food-chain. Since no dose-effect relationship has been found in humans, it cannot be excluded that DES could have been toxic at low doses, and that other less potent xenoestrogens would have similar effects.

These questions are reviewed here, and new hypotheses on the mechanisms of action of DES and the epidemiology of CCA are presented. In the light of their recently discovered effects on developmental gene expression, DES and similar xenoestrogens are more appropriately to be called hormonal disrupters than modulators. However, the picture is far from clear. With so many doubts about the most extensively studied of oestrogens, a fortiori, the only firm conclusion that the DES story allows us to draw, with regard to other xenoestrogens, is that it is under the precautionary principle that their diffusion into the environment deserves to be prevented. It is recommended that this be done with due regard to the psychological consequences of excessive alarm.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ashby, J., Tinwell, H., and Haseman, J. (1999) Lack of low-dose levels of bisphenol-A and diethylstilboestrol on the prostate gland of CF1 mice exposed in utero, Regul. Toxicol. Pharmacol. 30, 156–166.

    Article  CAS  Google Scholar 

  • Baird, D.D., Wilcox, A.J., and Herbst, A.L. (1996) Self-reported allergy infection and auto-immune diseases among men and women exposed in utero to diethylstilboestrol, J. Clin. Epidemiol. 49, 263–266.

    Article  PubMed  CAS  Google Scholar 

  • Beckman, W.C., Newbold, R.R., Teng, C.T., and McLachlan, J.A. (1994) Molecular feminisation of mouse seminal vesicle by prenatal exposure to diethylstilboestrol–Altered expression of messenger RNA, J. Urol. 151, 1370–1378.

    PubMed  Google Scholar 

  • Benhamou, B., Garcia, T., Lerouge, T., Vergezac, A., Gofflo, D., Bigogne, C., Chambon, P., and Gronemeyer, H. (1992) A single amino acid that determines the sensitivity of progesterone receptors to RU486, Science 255, 206–209.

    Article  PubMed  CAS  Google Scholar 

  • Bernheim, J., Goelen, G., Teugels, E., Vergote, I., and De Grüve, J. (2000) A BRCAnegative breast and ovarian cancer lineage with unexplained reversible repetitive spontaneous abortion, Eur. J. Cancer 36 Suppl. 4, 110.

    Google Scholar 

  • Bibbo, M., Al-Naqeeb, M., Baccarini, I., Gill, W., Newton, M., Sleeper, K.M., Sonek, M., and Wied, G.L. (1975) Follow-up study of male and female offspring of DES-treated mothers. A preliminary report, J. Reprod. Med. 15, 29–32.

    PubMed  CAS  Google Scholar 

  • Block, K., Kardana, A., Igarashi, P., and Taylor, H.S. (2000) In utero diethylstilboestrol (DES) alters Hox gene expression in the developing müllerian system, FASEB J. 14, 1101–1108.

    PubMed  CAS  Google Scholar 

  • Brackbill, Y., and Berendes, H.W. (1978) Dangers of diethylstilboestrol: Review of a 1953 Paper, Lancet 2, 520.

    Article  PubMed  CAS  Google Scholar 

  • Cagen, S.Z., Waechter, J.R., Dimond, S.S., Breslin, W.J., Butala, J.H., Jekat, F.W., Joiner, R.G., Shiotsuka, R.N., Veenstra, G.E., and Harris, L.R. (1999) Normal reproductive organ development in wistar rats exposed to bisphenol-A in the drinking water, Regul. Toxicol. Pharmacol. 30, 130–139.

    Article  PubMed  CAS  Google Scholar 

  • Cloitre, M., Ehrhardt, A.A., Verdiano, N.P., and Meyer-Bahlburg, H.F.L. (1988) The psychological impact of prenatal DES exposure in women: A comparison of short-term and long-term effects, J. Psychosom. Obstet. Gynaecol. 8, 149–168.

    Article  Google Scholar 

  • Couse, J.F., Davis, V.L., Hanson, R.B., Jefferson, W.N., McLachlan, J.A., Bullock, B.C., Newbold, R.R., and Korack, K.S. (1997) Accelerated onset of uterine tumours in transgenic mice with aberrant expression of the oestrogen receptor after neonatal exposure to diethylstilboestrol, Mol. Carcinog. 19, 236–242.

    Article  PubMed  CAS  Google Scholar 

  • Cunha, G.R. (1976) Epithelial-stromal interactions in development of the urogenital tract, Int. Rev. Cytology 47, 137–194.

    Article  CAS  Google Scholar 

  • Cunha, G.R. (1992) Role of mesenchyme in the development of the urogenital tract, NIH Workshop Long-Term Effects of Exposure to Diethylstilboestrol (DES), Virginia, USA, pp. 37–39.

    Google Scholar 

  • Dargent, D. (1991) Le DES syndrome - Quoi de neuf? Encycl. méd.-chir. 85 A, 10–16.

    Google Scholar 

  • Dargent, D., Arnould, P., and Mathevet, P. (1995) Adenocarcinome à cellules claires (ACCC) du vagin. Role du diethylstilboestrol (DES). Faits et hypotheses. Revue de la litterature à propos d’une série originale de 9 Cas. 1) Casuistique–Discussion nosographique, Jobgyn 3, 117–118.

    Google Scholar 

  • Dieckmann, W.J., Davis, M.E., Rynkiewicz, L.M., and Pottinger, R.E. (1953) Does the administration of diethylstilboestrol during pregnancy have therapeutic value ? Am. J. Obstet. Gynecol. 66, 1062–1081.

    PubMed  CAS  Google Scholar 

  • Dodds, E.C., and Lawson, W. (1936) Synthetic oestrogenic agents without the phenanthrene nucleus, Nature 137, 996.

    Article  CAS  Google Scholar 

  • Edelman, D.A. (1989) Diethylstilboestrol exposure and the risk of clear cell cervical and vaginal adenocarcinoma, Int. J. Fertil. 34, 251–255.

    PubMed  CAS  Google Scholar 

  • Ernst, H., Riebe, M., and Mohr, U. (1986) Undifferentiated sarcomas induced in Syrian hamsters by subcutaneous injection of diethylstilboestrol, Cancer Lett. 31, 181–186.

    Article  PubMed  CAS  Google Scholar 

  • Ferguson, J.H. (1953) Effect of stilboestrol on pregnancy compared to the effect of a placebo, M.J. Obstet. Gynecol. 65, 592–601.

    CAS  Google Scholar 

  • Fitzsimons, M.P. (1944) Gynaecomastia in stilboestrol workers, Br. J. Ind. Med. 1, 235–236.

    CAS  Google Scholar 

  • Giusti, R.M., Iwamoto, K., and Hatch, E.E. (1995) Diethylstilboestrol revisited: A review of the long-term health effects, Ann. Intern. Med. 122, 778–788.

    PubMed  CAS  Google Scholar 

  • Goldberg, J.M., and Facone, T. (1999) Effect of diethylstilboestrol on reproductive function, Fertil. Steril. 72, 1–7.

    Article  PubMed  CAS  Google Scholar 

  • Greenwald, P., Barlow, J.J., Nasca, P.C., and Burnett, W.S. (1971) Vaginal cancer after maternal treatment with synthetic oestrogens, N. Engl. J. Med. 285, 390–392.

    Article  PubMed  CAS  Google Scholar 

  • Gupta, C. (2000) Reproductive malformation of the male offspring following material exposure to oestrogenic chemicals, Proc. Soc. Exp. Biol. Med. 224, 61–68.

    Article  PubMed  CAS  Google Scholar 

  • Gustayson, C.R., Gustayson, J.C., Noller, K.L., O’Brien, P.C., Melton, L.J., Pumariega, A.J., Kaufman, R.H., and Colton, T. (1991) Increased risk of profound weight loss among women exposed to diethylstilboestrol in utero, Behay. Neural. Biol. 55, 307–312.

    Article  Google Scholar 

  • Hakem, R., de la Pompa, J.L., Sirard, C., Mo, R., Woo, M., Hakem, A., Wakeham, A., Potter, J., Reitmair, A., Billia, F., Firpo, E., Hui, C.C., Roberts, J., Rossant, J., and Mak, T.W. (1996) The tumour suppressor gene BRCA 1 is required for embryonic cellular proliferation in the mouse, Cell 85, 1009–1023.

    Article  PubMed  CAS  Google Scholar 

  • Hanselaar, A.G.J.M., Van Leusen, N.D.M., De Wilde, P.C.M., and Vooijs, G.P. (1991) Clear cell adenocarcinoma of the vagina and cervix. A report of the Central Netherlands Registry with emphasis on early detection and prognosis, Cancer 67, 1971–1978.

    Article  PubMed  CAS  Google Scholar 

  • Hanselaar, A.G.J.M., Van Loosbroek, M., Schuurbiers, O., Helmerhorst, T., Bulten, J., and Bernheim, J. (1997) Clear cell adenocarcinoma of the vagina and cervix: An update of the Central Netherlands Registry showing twin age incidence peaks, Cancer 79, 2229–2236.

    Article  PubMed  CAS  Google Scholar 

  • Hanselaar, A.G.J.M., Boss, E.K., Massuger, L.F.A.G., and Bernheim, J.L. (1999) Cytologic examination to detect clear cell adenocarcinoma of the vagina or cervix, Gynecol. Oncol. 75, 338–344.

    Article  PubMed  CAS  Google Scholar 

  • Hatch, E.E., Palmer, J.R., Titus-Ernstoff, L., Noller, K.L., Kaufman, R.H., Mittendorf, R., Robboy, S.J., flyer, M., Cowan, C.M., Adam, E., Colton, T., Hartge, P., and Hoover, R.N. (2000). Cancer risk in women exposed to diethylstilboestrol in utero, JAMA 280, 630–634.

    Article  Google Scholar 

  • Heinonen, O.P. (1973) Diethylstilboestrol in pregnancy. Frequency of exposure and usage patterns, Cancer 31, 573–577.

    Article  PubMed  CAS  Google Scholar 

  • Herbst, A.L., Ulfelder, H., and Poskanzer, D.C. (1971) Adenocarcinoma of the vagina. Association of maternal stilboestrol therapy with tumour. Appearance in young women, N. Engl. J. Med. 284, 878–881.

    Article  PubMed  CAS  Google Scholar 

  • Herbst, A., Hubby, M., Azizi, F. and Makii, M. (1981) Reproductive and gynaecologic surgical experience in diethylstilboestrol-exposed daughters, Am. J. Obstet. Gynecol. 141, 1019–1028.

    PubMed  CAS  Google Scholar 

  • Herbst, A.L. (1985) Letter to the editor, N. Engl. J. Med. 312, 1060.

    Google Scholar 

  • Herbst, A., Anderson, S., Hubby, M., Haenszel, W., Kaufman, R., and Noller, K. (1986) Risk factors for the development of diethylstilboestrol associated clear cell adenocarcinoma: a case-control study, Am. J. Obstet. Gynecol. 154, 814–822.

    PubMed  CAS  Google Scholar 

  • Hines, M., and Shipley, C. (1984) Prenatal exposure to diethylstilboestrol (DES) and the development of sexually dimorphic cognitive abilities and cerebral lateralisation, Dev. Psychol. 20, 81–94.

    Article  Google Scholar 

  • Howdeshell, K.L., Hotchkiss, A.K., Thayer, K.A., Vandenbergh, J.G., and vom Saal, F.S. (1999) Exposure to bisphenol-A advances puberty, Nature 401, 763–764.

    Article  PubMed  CAS  Google Scholar 

  • Huggins, C. (1967) Endocrine induced regression of cancers, Science 156, 1050–1054.

    Article  PubMed  CAS  Google Scholar 

  • IARC–International Agency for Research on Cancer (1979) IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man, Vol. 21, Sex Hormones (II), Lyon, France, pp. 173–231.

    Google Scholar 

  • Jamison, K.R. (1986) Suicide and bipolar disorders, in J.J. Mann and M. Stanley (eds), Psychobiology of Suicidal Behaviour, Ann. N.Y. Acad. Sci. 487, pp. 301–315.

    Google Scholar 

  • Karnaky, K.J. (1949) The effect of diethylstilboestrol “in the prolongation of pregnancy, Am. J. Obstet. Gynecol. 58, 596–598.

    PubMed  CAS  Google Scholar 

  • Katz, D.L., Frankenburg, F.R., Benowitz, L.I., and Gilbert, J.M. (1987) Psychosis and prenatal exposure to diethylstilboestrol, J. Nerv. Ment. Dis. 175, 306–308.

    Article  PubMed  CAS  Google Scholar 

  • Kaufman, R.H., Binder, G.L., Gray, P.M., and Adam, E. (1977) Upper genital tract changes associated with exposure in utero to diethylstilboestrol, Am. J. Obstet. Gynecol. 128, 51–59.

    PubMed  CAS  Google Scholar 

  • Kaufman, R., Adam, E., Binder, G., and Gerthoffer, E. (1980) Upper genital tract changes and pregnancy outcome in offspring exposed in utero to diethylstilboestrol, Am. J. Obstet. Gynecol. 137, 299–308.

    PubMed  CAS  Google Scholar 

  • Kerjean, A., Poirot, C., Epelboin, S., and Jouannet, P. (1999) Effect of in utero diethylstilboestrol exposure on human oocyte quality and fertilisation in a programme of in-vitro fertilisation, Human Reprod. 14, 1578–1581.

    Article  CAS  Google Scholar 

  • Kjörstad, K.E., Bergstrom, J., and Abeler, V. (1989) Clear cell adenocarcinoma of the cervix uteri and vagina in young women in Norway, Tidsskr. Nor. Loegeforen 109, 1634–1637.

    Google Scholar 

  • Labarthe, D., Adam, E., Noller, K.L., O’Brien, P.C., Robboy, S.J., Tilley, B.C., Townsend, D., Barnes, A.B., Kaufman, R.H., Decker, D.G., Fish, C.R., Herbst, A.L., Gundersen, J., and Kurland, K.T. (1978) Design and preliminary observations of national cooperative diethylstilboestrol adenosis (DESAD) project, Obstetr. Gynecol. 51, 453458.

    Google Scholar 

  • Lacassagne, A. (1938) Apparition d’adénocarcinomes mammaires chez des souris males traitées par une substance oestrogène synthétique, C. R. Soc. Biol. 129, 641–643.

    CAS  Google Scholar 

  • Lavigne, J.A., Helzlsauer, K.J., Huang, H.Y., Strickland, P.C., Bell, D.A., Selmin, O., Watson, M.A., Hoffman, S., Comstock, G.W., and Yager, J.D. (1997) An association between the allele coding for a low activity variant of catechol-O-methyltransferase and the risk for breast cancer, Cancer Res. 57, 5493–5497.

    PubMed  CAS  Google Scholar 

  • Lehrer, S., Sanchez, M., Song, K.H., Dalton, J., Levine, E., Savoretti, P., Thung, S.N., and Schachter, B. (1990) Oestrogen receptor B -region polymorphism and spontaneous abortion in women with breast cancer, Lancet 335, 622–624.

    Article  PubMed  CAS  Google Scholar 

  • Li, S., Washburn, K.A., Moore, R., Uno, R., Teng, C., Newbold, R.R., McLachlan, J.A., and Negishi, M. (1997) Developmental exposure to diethylstilboestrol elicits demethylation of oestrogen-responsive lactoferrin gene in mouse uterus, Cancer Res. 57, 4356–4359.

    PubMed  CAS  Google Scholar 

  • Liehr, J.G., Dague, B.B., Ballatore, A.M., and Henkin, J. (1983) Diethylstilboestrol (DES) quinone: A reactive intermediate in DES metabolism, Biochem. Pharmacol. 32, 3711–3718.

    Article  PubMed  CAS  Google Scholar 

  • Liehr, J.G., Avitts, T.A., Randerath, E., and Randerath, K. (1986) Oestrogen-induced endogenous DNA adduction: Possible mechanism of hormonal cancer, Proc. Natl. Acad. Sci. U.S.A. 83, 5301–5305.

    Article  PubMed  CAS  Google Scholar 

  • Liehr, J.G. (1990) Genotoxic effects of oestrogens, Mutat. Res. 238, 269–276.

    Article  PubMed  CAS  Google Scholar 

  • Liehr, J.G. (1994) Mechanisms of metabolic activation and inactivation of catecholoestrogens: A basis of enotoxicity, Polycyclic Aromatic Compounds 6, 229–239.

    Article  CAS  Google Scholar 

  • Lish, J.D., Ehrhardt, A.A., Meyer-Bahlburg, H.F., Rosen, L.R., Gruen, R.S., and Verdiano, N.P. (1991) Gender-related behaviour development in females exposed to diethylstilboestrol in utero: An attempted replication, J. Am. Acad. Child Adolesc. Psychiatry 30, 29–37.

    Article  PubMed  CAS  Google Scholar 

  • Lish, J.D., Meyer-Bahlburgh, H.F., Ehrhardt, A.A., Travis, B.C., and Veridiano, N.P. (1992) Prenatal exposure to diethylstilboestrol: Childhood play behaviour and adult gender-role behaviour in women, Arch. Sex. Behay. 21, 423–441.

    Article  CAS  Google Scholar 

  • Little, A.B. (1976) Proceedings US District Court, District of Massachusetts, pp. 1514–1515.

    Google Scholar 

  • Ma, L., Benson, G.V., Lim, H., Dey, S.K., and Maas, R.L. (1998) Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by oestrogen and progesterone and repression in mullerian duct by the synthetic oestrogen diethylstilboestrol (DES), Dev. Biol. 197, 141–154.

    Article  PubMed  CAS  Google Scholar 

  • Mantel, N. (1985) Some problems with investigations and epidemiologic studies relating to pregnancy, Prog. Clin. Biol. Res. 163, 45–48.

    Google Scholar 

  • Morgan, L., Crawshaw, S., Baker, P.N., Pipkin, F.B., and Kalsheker, N. (2000) Polymorphism in oestrogen response element associated with variation in plasma angiotensin concentrations in healthy pregnant women, J. Hypertens. 18, 553–557.

    Article  PubMed  CAS  Google Scholar 

  • Jarred, R.A., Cancilla, B., Prins, G.S., Thayer, K.A., Cunha, G.R., and Risbridger, G.P. (2000) Evidence that oestrogens directly alter androgen-regulated prostate development, Endocrinology 141, 3471–3477.

    Article  PubMed  CAS  Google Scholar 

  • Harnish, D.C., Scicchitano, M.S., Adelman, S.J., Lyttle, C.R., and Karathanasis, S.K. (2000) The role of CBP in oestrogen receptor cross-talk with nuclear factor-kappaB in HepG2 cells, Endocrinology 141, 3403–3411.

    Article  PubMed  CAS  Google Scholar 

  • Marselos, M., and Tomatis, L. (1992) Diethylstilboestrol: I, pharmacology, toxicology and carcinogenicity in humans, Eur. J. Cancer 28A (67), 1182–1189.

    Article  Google Scholar 

  • Marselos, M., and Tomatis, L. (1993) Diethylstilboestrol: II, pharmacology, toxicology and carcinogenicity in experimental animals, Eur. J. Cancer 29, 149–155.

    Article  Google Scholar 

  • McEwen, B.S. (1997) Hormones as regulators of brain development: Life-long effects related to health and disease, Acta Paediatr. 422, 41–44.

    Article  CAS  Google Scholar 

  • Mc Farlane, M.J., Feinstein, A.R., and Horwitz, R.I. (1986) Diethylstilboestrol and clear cell vaginal carcinoma. Reappraisal of the epidemiologic evidence, Am. J. Med. 81, 855–863.

    Article  PubMed  CAS  Google Scholar 

  • McLachlan, J.A., Newbold, R.R., Teng, C.T., and Korach, K.S. (1992) Environmental oestrogens: orphan receptors and genetic imprinting, Adv. Mod. Environm. Toxicol. 21, 107–112.

    CAS  Google Scholar 

  • McMartin, K.E., Kennedy, K.A., Greenspan, P., Alam, S.N., Greiner, P., and Yam, J. (1978) Diethylstilboestrol: A review of its toxicity and use as a growth promoter in food-producing animals, J. Environ. Pathol. Toxicol. 1, 279–313.

    PubMed  CAS  Google Scholar 

  • Melnick, S., Cole, P., Anderson, D., and Herbst, A. (1987) Rates and risks of diethylstilboestrol-related clear cell adenocarcinoma of the vagina and cervix. An update, N. Engl. J. Med. 316, 514–516.

    Article  PubMed  CAS  Google Scholar 

  • Meyer-Bahlburg, H.F.L., Ehrhardt, A.A., Endicott, J., Verdidiano, N.P., Whitehead, D., and Vann, F.H. (1985) Depression in adults with a history of prenatal DES exposure, Psychopharmacol. Bull. 21, 686–689.

    PubMed  CAS  Google Scholar 

  • Migliaccio, S., Newbold, R.R., McLachlan, J.A., and Korach, K.S. (1995) Alterations in oestrogen levels during development affects the skeleton: Use of an animal model, Environ. Health Perspect. 103 Suppl. 7 95–97.

    Google Scholar 

  • Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P.A., Harshman, K., and Fautigian, S. (1994) A strong candidate for breast and ovarian cancer susceptibility gene BRCA 1, Science 266, 66–71.

    Google Scholar 

  • Miksicek, R.J. (1994) Steroid receptor variants and their potential role in cancer, Semin. Canc. Biol. 5, 369–379.

    CAS  Google Scholar 

  • Miller, C., and Sassoon, D.A. (1998) Wnt-7a maintains appropriate uterine patterning during the development of the female mouse reproductive tract, Development 125, 3201–3211.

    PubMed  CAS  Google Scholar 

  • Miller, C., Pavlova, A., and Sassoon, D.A. (1998a) Differential expression patterns of Wnt genes in the murine female reproductive tract during development and the oestrous cycle, Mech. Dev. 76, 91–99.

    Article  PubMed  CAS  Google Scholar 

  • Miller, C., Degenhardt, K., and Sassoon, D.A. (1998b) Fetal exposure to DES results in deregulation of Wnt-7A during uterine morphogenesis, Nat. Genet. 20, 228–230.

    Article  PubMed  CAS  Google Scholar 

  • Nagel, S.C., vom Saal, F.S., Thayer, K.A., Dhar, M.G., Boechler, M., and Welshons, W.V. (1997) Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol-A and octylphenol, Environ. Health Perspect. 105, 70–76.

    Article  PubMed  CAS  Google Scholar 

  • Nelson, K.G., Sakai, Y., Eitzman, B., Steed, T., and McLachlan, J.A. (1994) Exposure to diethylstilboestrol during a critical developmental period of the mouse reproductive tract leads to persistent induction of two oestrogen-regulated genes, Cell Growth Differ. 5, 595–606.

    PubMed  CAS  Google Scholar 

  • Newbold, R.R., Pentecost, B.T., Yamashita, S., Lum, K., Miller, J.V., Nelson, P., Blair, J., Kong, H., Teng, C., and McLachlan, J.A. (1989) Female gene expression in the seminal vesicle of mice after prenatal exposure to diethylstilboestrol, Endocrinology 124, 2568–2576.

    Article  PubMed  CAS  Google Scholar 

  • Newbold, R.R., Jefferson, W.N., Padilla-Burgos, E., and Bullock, B.C. (1997) Uterine carcinoma in mice treated neonatally with tamoxifen, Carcinogenesis 18, 2293–2298.

    Article  PubMed  CAS  Google Scholar 

  • Newbold, R.R., Hanson, R.B., Jefferson, W.N., Bullock, B.C., Haseman, J., and McLachlan, J.A. (1998) Increased tumours but uncompromised fertility in the female descendants of mice exposed developmentally to diethylstilboestrol, Carcinogenesis 19, 1655–1663.

    Article  PubMed  CAS  Google Scholar 

  • Newbold, R.R., Jefferson, W.N., Hanson, R.B., Padilla-Banks, E., Bullock, B.C., and McLachlan, J.A. (1999) Increased tumour prevalence in DES-lineage mice, Proceedings DES Research Update, NCI, NIH.

    Google Scholar 

  • O’Brien, P.C., Noller, K.L., Robboy, S.J., Barnes, B., Kaufman, R.H., Tilley, B.C., and Townsend, D.E. (1979) Vaginal epithelial changes in young women enrolled in the National Co-operative Diethylstilboestrol Adenosis (DESAD) Project, Obstet. Gynecol. 53, 300–308.

    PubMed  Google Scholar 

  • Palmer, J.R., Anderson, D., Nelwrich, S.P., and Herbst, A.L. (2000) Risk factors for diethylstilboestrol-associated clear cell adenocarcinoma, Obstet. Gynecol. 95, 814–820.

    Article  PubMed  CAS  Google Scholar 

  • Pavlova, A., Boutin, E., Cunha, G., and Sassoon, D. (1994) Msx 1 (Hox-7.1) in the adult mouse uterus: cellular interactions underlying regulation of expression, Development 120, 335–346.

    PubMed  CAS  Google Scholar 

  • Reinisch, J.M., and Sanders, S.A. (1984) Prenatal gonadal steroidal influences on gender-related behaviour, Prog. Brain Res. 61, 407–416.

    Article  PubMed  CAS  Google Scholar 

  • Salahifar, H., Baxter, R.C., and Martin, JL. (2000) Differential regulation of insulin-like growth factor-binding protease activity in MCF-7 breast cancer cells by oestrogen and transforming growth factor ßl, Endocrinology 141, 3104–3110.

    Article  PubMed  CAS  Google Scholar 

  • Sangvai, M., Thie, J., and Hofmann, G.E. (1997) The effect of intrauterine diethylstilboestrol exposure on ovarian reserve screening, Am. J. Obstet. Gynecol. 177, 568–572.

    Article  PubMed  CAS  Google Scholar 

  • Sassoon, D. (1999) Wnt genes and endocrine disruption of the female reproductive tract: A genetic approach, Mol. Cell Endocrinol. 158, 1–5.

    Article  PubMed  CAS  Google Scholar 

  • Senekjian, E., Frey, K., Anderson, D., and Herbst, A. (1988) Infertility among daughters either exposed or not exposed to diethylstilboestrol, Am. J. Obstet. Gynecol. 158, 493–498.

    PubMed  CAS  Google Scholar 

  • Sharp, G.B., and Cole, P. (1991) Identification of risk factors for diethylstilboestrol. Associated clear cell adenocarcinoma of the vagina: Similarities to endometrial cancer, Am. J. Epidemiol. 134, 1316–1324.

    PubMed  CAS  Google Scholar 

  • Sheehan, D.M., Willingham, E., Gaylor, D., Bergeron, J.M., and Crews, D. (1999) No threshold dose for oestradiol-induced sex reversal of turtle embryos: How little is too much? Environ. Health Perspect. 107, 155–159.

    Article  PubMed  CAS  Google Scholar 

  • Smith, G.V., and Smith, O.W. (1948) Internal secretions and toxemia of late pregnancy, Physiol. Rev. 28, 1–22.

    PubMed  CAS  Google Scholar 

  • Smith, O.W., Smith, G.W.S., and Hurwitz, D. (1944) Relationship between hormonal abnormalities and accidents of late pregnancy in diabetic women, Am. J. Med. Sci. 208, 25–29.

    Article  CAS  Google Scholar 

  • Smith, O.W. (1948) Diethylstilboestrol in the prevention and treatment of complications of pregnancy, Am. J. Obstet. Gynecol. 56, 821–827.

    PubMed  CAS  Google Scholar 

  • Smith, O.W., and Smith, G.V. (1949a) Use of diethylstilboestrol to prevent fetal loss from complications of late pregnancy, N. Engl. J. Med. 241, 562–568.

    Article  PubMed  CAS  Google Scholar 

  • Smith, O.W., and Smith, G.V. (1949b) The influence of diethylstilboestrol on the progress and outcome of pregnancy as based on a comparison of treated with untreated primigravidas, Am. J. Obstet. Gynecol. 58, 994–1009.

    PubMed  CAS  Google Scholar 

  • Spearow, J.L., Doemeny, P., Sera, R., Leffler, R., and Berkley, M. (1999) Genetic variation in susceptibility to endocrine disruption by oestrogen in mice, Science 285, 1259–1261.

    Article  PubMed  CAS  Google Scholar 

  • Spira, A., Goujard, J., Henrion, R., Lemerle, J., Robel, P., and Tchobroutsky, C. (1983) L’administration de diethylstilboestrol (DES) pendant la grossesse, un problème de santé publique. Diethylstilboestrol (DES) during pregnancy, a public health problem, Rev. Epidem. Santé Publ. 31, 249–272.

    CAS  Google Scholar 

  • Storment, J.M., Meyer, M., and Osol, G. (2000) Oestrogen augments the vasodilatry effects of vascular endothelial growth factor in the uterine circulation of the rat, Am. J. Obstet. Gynecol. 189, 449–453.

    Article  Google Scholar 

  • Thayer, K., Howdeshell, K., Ruhlen, R., vom Saal, F., Lubahn, D., Buchanan, D., Cooke, P., and Welshons, W. (1999) Low-dose effects following prenatal exposure to oestrogen, DES Research Update 1999: Current Knowledge, Future Directions, Bethesda, USA, p. 61.

    Google Scholar 

  • Turusov, V.S., Trukhanova, L.S., Parfenov, Y.D., and Tomatis, L. (1992) Occurrence of tumours in the descendents of CSA male mice prenatally treated with diethylstilboestrol, Int. J. Cancer 50, 131–135.

    Article  PubMed  CAS  Google Scholar 

  • Valentine, J.E, Kalkhoven, E., White, R., Hoare, S., and Parker, M.G. (2000) Mutations in the oestrogen receptor ligand binding domain discriminate between hormone-dependent transactivation and transrepression, J. Biol. Chem. 275, 25322–25329.

    Article  PubMed  CAS  Google Scholar 

  • Vessey, M., Fairweather, D., Norman-Smith, B., and Buckley, J. (1983) A randomised double-blind controlled trial of the value of stilboestrol therapy in pregnancy: longterm follow-up of mothers and their offspring, Br. J. Obstet. Gynaecol. 90, 1007–1017.

    Article  PubMed  CAS  Google Scholar 

  • vom Saal, F.S., Timms, B.G., Montano, M.M., Palanza, P., Thayer, K.A., Nagel, S.C., Dhar, M.D., Ganjam, V.K., Parmigiani, S., and Welshons, W. (1997) Prostate enlargement in mice due to fetal exposure to low doses of oestradiol or diethylstilboestrol and opposite effects at high doses, Proc. Natl. Acad. Sci. U.S.A. 94, 2056–2061.

    Article  Google Scholar 

  • Walker, B.E. (1984) Tumours of female offspring of mice exposed prenatally to diethylstilboestrol, J. Natl. Cancer Inst. 73, 133–140.

    PubMed  CAS  Google Scholar 

  • Walker, B.E., and Haven, M.I. (1997) Intensity of multigeneration carcinogenesis from diethylstilboestrol in mice, Carcinogenesis 18, 791–793.

    Article  PubMed  CAS  Google Scholar 

  • Welshons, W.V., Nagel, S.C., Thayer, K.A., Judy, B.M., and vom Saal, F.S. (1999) Low-dose bioactivity of xenoestrogens in animals: Fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice, Toxicol. Ind. Health 15, 12–25.

    Article  PubMed  CAS  Google Scholar 

  • Williams, T.J., Pepitone, M.E., Christensen, S.E., Cooke, B.M., Huberman, A.D., Breedlove, N.J., Breedlove, T.J., and Jordan, C.L. (2000) Finger-length ratios and sexual orientation, Nature 404, 455.

    Article  PubMed  CAS  Google Scholar 

  • Young C.L. (1978) Diethylstilboestrol; A Cancer Control Monograph, SRI International, Chemical Industries Center, Stanford, CA, USA.

    Google Scholar 

  • Zhu, B.T., and Conney, A.H. (1998) Functional role of oestrogen metabolism in target cells: review and perspectives, Carcinogenesis 19, 1–29.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine Human Ecology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussel, Belgium

    Jan L. Bernheim

Authors
  1. Jan L. Bernheim
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical School, Department of Pathology, National and Capodistrian University of Athens, 75, Mikras Asias, Goudi, 11527, Athens, Greece

    Polyxeni Nicolopoulou-Stamati (ASPIS Project Co-ordinator) (ASPIS Project Co-ordinator)

  2. Human Ecology Department, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussel, Belgium

    Luc Hens

  3. Fetal and Infant Toxico-Pathology, University of Liverpool, Mulberry Street, L69 7ZA, Liverpool, UK

    C. V. Howard

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Bernheim, J.L. (2001). The ‘Des Syndrome’: A prototype of Human Teratogenesis and Tumourigenesis by Xenoestrogens?. In: Nicolopoulou-Stamati, P., Hens, L., Howard, C.V. (eds) Endocrine Disrupters. Environmental Science and Technology Library, vol 18. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9769-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-94-015-9769-2_5

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5729-7

  • Online ISBN: 978-94-015-9769-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation