Plastic Compounds and Birth Control Estrogen Cause Prostate Abnormalities in Mice

Catherine A. Richter, Ph.D. and Frederick S. vom Saal, Ph.D.
University of Missouri, Columbia
F32ES11549 and R01ES11283

Background: Human fetuses can be exposed to man-made estrogen-like substances through a variety of sources. Each year approximately 3% of all women taking birth-control pills become pregnant; thus exposing their unborn children to small doses of ethinylestradiol. Exposure to another estrogen-like compound, bisphenol A, can occur through leaching from polycarbonate plastic products and from the linings of cans containing food and beverages.

Exposures to these and other so-called environmental estrogens have been linked to a variety of reproductive and developmental disorders in humans and animals. For more than 60 years, scientists have postulated that male fetuses exposed to elevated estrogen levels may be at risk for enlarged prostate glands much later in life. This is an example of the Fetal Basis of Adult Disease theory that is gaining momentum and concern in the scientific community and is a major research effort for NIEHS (to read more visit http://www3.interscience.wiley.com/cgi-bin/fulltext/109934129/PDFSTART) (http://www3.interscience.wiley.com/cgi-bin/fulltext/109934129/PDFSTART)) .

Advance: A team of NIEHS-supported researchers at the University of Missouri, Columbia fed pregnant mice either of the aforementioned chemicals mixed in corn oil. Both compounds produced an increase in the number and size of prostate ducts in the male offspring, which appeared to be caused by elevated proliferation of basal epithelial cells in the primary prostate ducts. Exposure to these two chemicals also caused a malformation of the urethra near the neck of the bladder. The researchers noted that these two effects are identical to those caused by the synthetic estrogen diethylstilbestrol, which is a known carcinogen. However, it is not known whether these effects would lead to prostate cancer in this model.

Implications: Since both bisphenol A and ethinylestradiol are known to cross the placenta and enter the fetus, these results may have direct implications on human health. The dose of ethinylestradiol used in the experiment was actually lower than that of women taking oral contraception. The bisphenol A dose used produced fetal levels lower than those seen in human fetuses at birth. Therefore this experiment is highly relevant to everyday human exposures. The study authors conclude that these effects "warrant a thorough reevaluation of risks posed by doses of both ethinylestradiol and bisphenol A below those to which human fetuses are exposed."

Citation: Timms BG, Howdeshell KL, Barton L, Bradley S, Richter CA, Vom Saal FS. Estrogenic chemicals in plastic and oral contraceptives disrupt development of the fetal mouse prostate and urethra. Proc Natl Acad Sci U S A. 2005 May 10;102(19):7014-9.