EDCs : Developmental Programming and Fetal Origins of Adult Disease ; The DES Diethylstilbestrol Example

Abstract

Prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen and thus EDC, provides an unfortunate example of developmental programming. DES was given to U.S. pregnant women between 1938 and 1971 under the erroneous assumption that it would prevent pregnancy complications. In fact, in utero exposure to DES alters the normal programming of gene families, such as Hox and Wnt, that play important roles in reproductive tract differentiation. As a result, female offspring exposed to DES in utero are at increased risk of clear cell adenocarcinoma of the vagina and cervix, structural reproductive tract anomalies, infertility and poor pregnancy outcomes, while male offspring have an increased incidence of genital abnormalities and a possibly increased risk of prostate and testicular cancer. These observed human effects have been confirmed in numerous animal models which have also provided information on the toxic mechanisms of DES. Animal experiments have also predicted changes later found in DES-exposed humans, such as oviductal malformations, increased incidence of uterine fibroids and second-generational effects such as increased menstrual irregularities and possibly ovarian cancer in DES-granddaughters and increased hypospadias in DES-grandsons.

DES is but one example of how exposure to EDCs can disrupt developing organ systems and cause abnormalities, many of which only appear much later in life or in the subsequent generation, such as endometriosis, fibroids and breast, cervical and uterine cancer in women; poor sperm quality and increased incidence of cryptorchidism and hypospadias in men; and subfertility and infertility in men and women.

Sources

• NCBI, PMID: 18275883, 2008 Feb;89(2):281-300. doi: 10.1016/j.fertnstert.2007.10.002.
• PMC, Proceedings of the Summit on Environmental Challenges to Reproductive Health and Fertility: executive summary, PMC2440710, Feb 1, 2009.

More DES DiEthylStilbestrol Resources

• DES studies on cancers and screening.
• DES studies on epigenetics and transgenerational effects.
• DES studies on fertility and pregnancy.
• DES studies on gender identity and psychological health.
• DES studies on in-utero exposure to DES and side-effects.
• DES studies on the genital tract.
• Papers on DES lawsuits.
• DES videos and posts tagged DES, the DES-exposed, DES victims.