DES immunotoxic effects : selective diminution of T lymphocyte progenitors in fetal liver

Diethylstilbestrol (DES) causes hematopoietic hypocellularity and hepatocellular changes in murine fetal liver, affects gene expression

2007 Study Abstract

TCDD and DES have immunotoxic effects, including selective diminution of T lymphocyte progenitors in the fetal liver. The histologic presentation of fetal liver after exposure to either chemical has not been described. Similarly, limited information exists regarding mechanisms by which TCDD or DES may alter fetal hematopoiesis.

Treatment of pregnant C57BL/6 mice with either 10 micro g/kg/day TCDD or 48 micro g/kg/day DES on gestation days (gd) 14 and 16 led to increased fetal liver weight on gd 18. Moderate anisocytosis and anisokaryosis with increased cytoplasmic and nuclear sizes, and increased cytoplasmic basophilia were present within hepatocytes after TCDD or DES. Both chemicals also decreased the presence of hematopoietic cells, however megakaryocyte numbers were unaffected. In contrast to these similar outcomes, real time quantitative PCR using a preliminary panel of 4 genes suggested that the chemicals act through different gene targets.

TCDD increased c-jun gene expression in fetal liver, and decreased p53 without alteration in bcl-2 expression, indicating possible pro-proliferative and antiapoptotic effects.

DES decreased c-jun and bcl-2, without altering p53, suggesting a shift away from proliferation.

Both agents decreased PKCalpha expression, which may suggest shared decreased phosphorylation of substrates required for normal cell cycle progression.

Sources and more information
  • 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or diethylstilbestrol (DES) cause similar hematopoietic hypocellularity and hepatocellular changes in murine fetal liver, but differentially affect gene expression, Toxicologic pathology, NCBI PubMed PMID: 17943652, 2007 Oct.
  • Featured image credit res.cloudinary.
DES DIETHYLSTILBESTROL RESOURCES

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