Developmental programming : DES exposure induces changes in the expression of several uterine genes

Fetal and Early Postnatal Environmental Exposures and Reproductive Health Effects in the Female

This 2009 review presents current research into the role of the environment in normal female reproductive function and pathogenesis, specifically focusing on the ovary and uterus.

Abstract

Environmental Factors in Uterine Pathologies

From the 1940s to 1970s, the xenoestogen DES was extensively prescribed to pregnant women at risk for miscarriage. Women exposed to DES in utero during critical periods of reproductive tract development developed several types of reproductive tract abnormalities, as well as an increased incidence of cervical-vaginal cancer later in life.

Animal studies that simulate the human DES experience have since shown that exposure of the developing reproductive tract of CD-1 mice to DES imparts a permanent estrogen imprint that alters reproductive tract morphology, induces persistent expression of the lactoferrin and c-fos genes and induces a high incidence of uterine adenocarcinoma.

Since DES is readily metabolized and cleared within days after exposure, the persistent alterations resulting from developmental DES exposure cannot simply be explained by residual body burden of the compound. DES exposure also induces changes in the expression of several uterine genes involved in tissue patterning, such as Wnt7a, Hoxa9, Hoxa10 and Hoxa11, contributing to changes in tissue architecture and morphology. DES-induced developmental programming appears to require the estrogen receptor α (ERα), suggesting that signaling through this receptor is crucial for establishing developmental programming. These initial observations with DES firmly established the developmental period as a window of susceptibility during which an inappropriate xenoestrogen exposure can induce developmental programming and increase risk for diseases, including cancer, later in life.

Sources

  • Full study (free access) : Fetal and early postnatal environmental exposures and reproductive health effects in the female, Fertility and sterility, NCBI PubMed, PMC2527475, 2009 Feb 1.
  • Featured image credit h heyerlein.
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