Fetal Dioxin Exposure Seen to Increase Risk of LUTS Development in Adult Mice

Fetal Dioxin Exposure Seen to Increase Risk of LUTS Development in Adult Mice

A study published in the journal Toxicological Sciences found that exposure to the common environmental pollutant 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increased the risk of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) in genetically susceptible mice.

TCDD, often referred to simply as dioxin, is one of the most widely spread environmental toxins. It is present in drinking water and, according to the U.S. Environmental Protection Agency, stems in large part from backyard burning of waste as well as from manufacturing and refining processes. The chemical is highly toxic and only slowly eliminated from the body, so that exposure to even the low amounts found in the environment are potentially dangerous for human health. The half-life of TCDD in humans is 7–11 years, and experimental animals exposed to higher levels have a delayed or incomplete prostate development. The chemical also increases cancer risk.

Evidence for a fetal origin of prostatic disease is beginning to emerge. To test whether genetically susceptible mice would develop more severe LUTS following TCDD exposure, University of Wisconsin researchers used a mouse with mutations predisposing it to prostate hyperplasia. Pregnant mice received one single dose of TCDD that was low enough not to cause a disruption in prostate development, but high enough to remain in the mice pups throughout weaning.

When male mice were adult, some were also exposed to higher levels of testosterone and estradiol in doses that are known to cause urinary disturbance in mice, and were then allowed to live for four more months. According to the report — titled In utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood — the mice that were exposed to TCDD alone had a reduced voiding pressure. Otherwise, TCDD exposure had little effect on the lower urinary tract anatomy or function.

In contrast, all the mice exposed both to TCDD and hormones had extensive changes in both function and anatomy, with increased kidney, bladder, prostate, and seminal vesicle weight. They also showed signs of kidney swelling due to build up of urine, and had a higher rate of prostate epithelial cell expansion, thickened prostate smooth muscle, and altered prostate and bladder collagen fiber distribution.

The authors suggest that increased risk of prostate hyperplasia-related LUTS results from an altered sensitivity to sex hormones by TCDD exposure in genetically susceptible mice.

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