General Obstetrics and Gynecology: Gynecology
Altered immune response in adult women exposed to diethylstilbestrol in utero,☆☆

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Abstract

Objective: Between 1940 and 1970, 1.5 million female fetuses were exposed to diethylstilbestrol in utero. Numerous deleterious effects on reproductive anatomic and physiologic characteristics have been documented in these women. However, the effects of this exposure on nonreproductive systems, which may have lifelong consequences as this cohort of women progresses beyond the childbearing years, have received little attention. On the basis of an earlier preliminary observation of altered immune reponse, we hypothesized that diethylstilbestrol-exposed women may show abnormalities in T-cell–mediated immune response. Study Design: Thirteen women exposed to diethylstilbestrol in utero were compared with 13 age- and menstrual cycle phase–matched control subjects with respect to the in vitro T-cell response to the mitogens phytohemagglutinin, concanavalin A, and interleukin 2. Results: As compared with controls, tritiated thymidine incorporation by T cells harvested from diethylstilbestrol-exposed women was increased 3-fold over a range of concentrations in response to concanavalin A (P <.001), increased by 50% over a range of concentrations in response to phytohemagglutinin (P <.001), and increased 2-fold in response to the endogenous mitogen interleukin 2 (P <.05). Conclusions: In vitro evidence suggests that women exposed to diethylstilbestrol have alterations in T-cell–mediated immunity. These changes require further attention with regard to their characterization, their role in the pathogenesis of cancer and autoimmunity, and their presence in normal women exposed to diethylstilbestrol in utero. (Am J Obstet Gynecol 2001;185:78-81.)

Section snippets

Subjects

Thirteen women with a well-documented history of in utero DES exposure (mean age, 39 years; range, 27-43 years) were compared with 13 age-matched control subjects. The DES-exposed women were selected from a group, which had been followed up prospectively from childhood by one of the authors (Louis Burke). All of the DES-exposed women had evidence of anomalies consistent with DES exposure, including cervical “hoods,” vaginal constriction rings, and vaginal adenosis.7, 8 Three were parous and 10

Results

Incorporation of thymidine labeled with tritium into peripheral blood mononuclear cells from both DESexposed women and control subjects exhibited a clear dose-response effect with increasing concentrations of both PHA and CON-A (P <.001). The magnitude of this response was such that the incorporation of thymidine labeled with tritium was 3-fold greater at the highest concentration of PHA (7.5 μg/mL) than at the lowest (1 μg/mL) and was 5-fold greater at the highest dose of CON-A (2.5 μg/mL)

Comment

Our data demonstrate that T cells from women exposed to DES in utero exhibit a marked increase in their response to stimulation from a variety of mitogens. This was true for the experiments using PHA, CON-A, and hrIL-2, all of which demonstrated remarkably consistent results.

The results of this study are particularly interesting in that they initially appear contrary to those that would be predicted by animal and human studies. Perinatal or adult exposure of rodents to estrogen treatment

Acknowledgements

We acknowledge and thank Jane Marchiori, MD, for her help in the laboratory in the analysis of the blood samples.

References (24)

  • EV. Rothenberg

    The development of functionally responsive T cells

    Adv Immunol

    (1992)
  • S Melnick et al.

    Rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix. An update

    N Engl J Med

    (1987)
  • Cited by (0)

    Reprint requests: Louis Burke, MD, Department of Obstetrics, Gynecology and Reproductive Biology and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215.

    ☆☆

    Deceased.

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