How does diethylstilbestrol DES cause reproductive tract abn

How does diethylstilbestrol (DES) cause reproductive tract abnormalities in the daughters of mothers given DES during pregnancy? What important transcription factors are involved?

(essay question)

Solution

Diethylstilbestrol (DES) is a synthetic estrogen and classified as an endocrine disruptor. Exposure to DES may occur through diet or medical treatment of breast and prostate cancers, hormone replacement therapy, Gonorrheal vaginitis, recurrent miscarriage etc. In early 40\'s pregnant women were prescribed DES for overcoming the danger of miscarriage,.

DES is potential teratogen ( agent causing malformations in the unborn foetus exposed in utero), and has been shown to cause a rare vaginal tumor and breast cancer in girls and young women who were exposed to this compound in utero. Daughters exposed to DES during pregnancy has higher risk of vaginal/cervical clear cell adenocarcinoma. There are also reports of its documented risk in male child exposed in utero.

Several signaling factors expressing in the epithelial and mesenchyma cells are essential for the deveopment of mammary glads of foetus. Exposure to DES in utero or neonatal exposure alters fetal mammary gland development in humans and other animals. This is because estrogens modify the developmental by interacting with various signaling factors such as Wnt/-catenin pathway, bone morphogenic protein 4, parathyroid hormone-related protein and the IGF family. DES exposure also causes changes in NF-kB signaling pathways and ERK pathways at the onset of puberty. Both these transcription factors are linked to breast cancer progression.