Third generation offspring – granddaughters and grandsons

Current perspective of diethylstilbestrol (DES) exposure in mothers and offspring

Highlights

  • Diethylstilbestrol (DES) is a synthetic, non-steroidal estrogen of the stilbestrol group acting as an endocrine disruptor.
  • Adverse pregnancy outcomes, infertility, cancer, and early menopause have been identified in women exposed to DES, their offspring, and subsequent generations.
  • DES is one of the major disasters in medicine and it is mandatory to tackle and promote programs of DES-related cancer prevention.

2017 Review Abstracts

Diethylstilbestrol (DES) was an orally active estrogen prescribed to the pregnant women to prevent miscarriages. DES is known as a ‘biological time bomb’ and long-term effects of DES have been recorded in the mothers exposed to DES and their offspring (DES-daughters and DES-sons). Adverse pregnancy outcomes, infertility, cancer, and early menopause have been discovered in women exposed to DES, and some events occur in their offspring and subsequent generations. An increased risk of breast cancer is not limited to the DES-exposed daughters.

We were told that it “could take over 50 years” to detect the effects of DES exposure in future generations, due to the length of time required for diseases to manifest. It is predicted that cross-generational responses to the exposure of DES are possible due to epigenetic changes in the DNA.

The studies on the cohort of grandchildren (grandsons and granddaughters) whose mothers were exposed to DES prenatally (i.e., grandchildren had no direct DES exposure) are limited as they have just reached the age when relevant health problems could be studied.

It seems that the DES 3rd generation has also an increased risk for cancer. The epigenetic effects of DES could be manifested in this generation. DES could affect daughters of the exposed mothers as their oocytes might be developing at the critical stage, but transgenerational effect of DES, i.e., children of sons or daughters of DES mothers, may have an epigenetic basis.

In opposition to developmental epigenetics transgenerational epigenetics implies an absence of resetting of epigenetic states between generations. In fact,the exposure to endocrine disruptor chemical compounds is associated with abnormal DNA methylation and other epigenetic modifications, as well as altered expression of genes important for development and function of reproductive tissues as recently observed by Ho et al.

In a multi-center study, an increase of congenital disabilities in the sons and daughters of the 3rd generation was observed. Currently, there are no large human studies that show adverse events of DES for granddaughters. Kaufman et al. conducted a small cohort study on 28 DES granddaughters and found neither CCA nor abnormalities of the lower genital tract. On the other hand, granddaughters may have more menstrual problems and higher infertility rate compared to non-exposed granddaughters. Direct maternal DES exposure during pregnancy can cause not only an alteration to the reproductive capacity of the woman, but also this alteration may be passed on to next generation, a phenomenon that is called ‘DES granddaughter effect’ and DES granddaughters may also harbor a higher risk of ovarian cancer rather than breast cancer. In DES grandsons, the incidence of hypospadia is 20 times higher than unexposed grandsons, but the risk of developing such anomaly seems to be low.

There is an urgent need to find ways to stop the inheritance cycle of DES and prevent adverse effects of DES in the future generations. The present article reviews the health implications of DES exposure and screening exams currently recommended to DES daughters and their offspring.

Sources

  • Current perspective of diethylstilbestrol (DES) exposure in mothers
    and offspring
    , NCBI PubMed, 28461243, August 2017.
  • Image credit gstatic.
DES DIETHYLSTILBESTROL RESOURCES

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