Immunomodulatory Effects of Diethylstilbestrol During Prenatal and Adult Life
Fenaux, Jillian Beth
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For nearly forty years diethylstilbestrol (DES) was administered to pregnant women to maintain healthy pregnancies. During this time, it is estimated that several million men and women have been exposed to DES during sometime of their life. The most common period of exposure was during fetal development. Although rarely used for the maintenance of pregnancy now, its current medical use is restricted to certain clinical situations such as breast and prostate cancer therapies in adults. Thus, DES exposure spans the entire lifetime, from prenatal to geriatric age. Since the early 1950s, health risks were beginning to be associated with prenatal DES treatment. So far only reproductive problems such as infertility, neoplastic diseases of the cervix and vagina and testicular cancers have been well-documented in DES cases. Immunological abnormalities associated with DES are only now beginning to be recognized. Self-reported cases and questionnaire-based studies have revealed increased incidence of infections and autoimmune diseases in DES exposed people. Animal studies that have examined the immunological effects of DES treatment are largely restricted to one gender, or to one dose of DES or to the developmental period. This is an important issue since human exposure to DES occurred in both men and women, at all ages and, at a wide-range of doses. The purpose of these studies was to investigate the immunological consequences resulting from the exposure to DES. Since sensitivity can vary between genders, dose and at the time of exposure, it is critical to investigate the DES-induced immunological changes during all stages of life in both genders. To address these critical gaps in the literature, we examined the immunomodulatory effects of adult and prenatal exposure to DES in males and females. Our findings show that DES effects were evident in both the thymus and spleen. DES markedly affected the apoptosis of thymocytes and the ability of splenic lymphocytes to proliferate in response to stimulants and secrete vital cytokines such as interferon-gamma. Our notable findings were that in-utero exposure to DES resulted in profound alterations in lymphocyte functionality, which were noticed as late as one-year of age. This suggests that alterations to the in utero environment can have deleterious consequences that may be long lasting. These studies have profound implications to the humans and animals exposed to DES, and indirectly to a whole range of other estrogenic compounds.
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