Perinatal Diethylstilbestrol Exposure and Autoimmune Disease

Animal studies have suggested that prenatal DES exposure may alter immune system development and function

Abstract

… “Diethylstilbestrol DES, a synthetic nonsteroidal compound possessing estrogenic activity, may have possible adverse effects on the postnatal human immune system after in utero exposure in women.

As an example, altered NK and T lymphocyte function in women exposed to DES in utero has been reported. In addition, Noller et al. have demonstrated an increased incidence of autoimmune diseases in women exposed in utero to DES. While it appears that estrogens mediate certain of their immune effects at the thymic level by altering thymic epithelium-dependent mechanisms, little is understood about mechanisms by which estrogenic chemicals may influence immune responses to foreign or self-antigens.

An increased risk of developing autoimmune disease in mice has been associated with altered prenatal hormonal environment. It has also been suggested that humans exposed in utero to DES may display a hyperreactive immune response. A retrospective study of DES-exposed (1711 individuals) and unexposed (922 individuals) cohorts examined the possibility that prenatal DES may affect the prevalence of autoimmune disease and found a positive correlation when autoimmune diseases were grouped. Specifically, the overall frequency of any autoimmune disease among exposed women was 28.6 per 1000 compared to 16.3 per 1000 among the controls (significantly different at p=0.02). Autoimmune diseases evaluated included systemic lupus erythematosus, scleroderma, Grave’s disease, Hashimoto’s thyroiditis, pernicious anemia, myasthenia gravis, thrombocytopenic purpura, rheumatoid arthritis, regional enteritis, chronic ulcerative colitis, multiple sclerosis, chronic lymphocytic thyroiditis, Reiter’s syndrome, and optic neuritis. However, only Hashimoto’s thyroiditis occurred significantly more often in the exposed women (p=0.04) when these autoimmune diseases were considered individually. A similar evaluation of 1173 humans exposed to DES during development (1079 daughters and 94 sons) found increased rates of asthma, arthritis, and diabetes mellitus compared to the general population . In a more recent study evaluating rates of allergy, infection, and autoimmune disease in DES-exposed sons and daughters (253 men and 296 women) matched with similar unexposed individuals (241 men and 246 women), no differences in disease occurrence were detected. These authors concluded that a larger sample was needed to evaluate DES-associated risk of autoimmunity since autoimmune diseases are relatively rare in the human population.

Data from humans in the preliminary studies above suggest the possibility that exposure to DES in utero may result in postnatal immune alterations, including increased autoimmune disease. However, the difficulty with continued surveillance of DES-exposed sons and daughters required for more definitive statements will become more difficult as this cohort ages and members are lost. This makes laboratory rodent studies important to determine if prenatal exposure to chemicals such as DES may predispose an individual to postnatal autoimmunity via alteration of development of immune cells. Animal models will also be necessary to answer questions regarding specific immune cell targets and mechanisms of action resulting from such exposures.” …

… read Perinatal Estrogen Exposure Diethylstilbestrol, Arthritis Research, Immune System, arthritisresearch, 19 Dec 2016.

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