Elsevier

Urology

Volume 70, Issue 3, September 2007, Pages 618-621
Urology

Basic Science
Endocrine Disruptors and Hypospadias: Role of Genistein and the Fungicide Vinclozolin

https://doi.org/10.1016/j.urology.2007.05.004Get rights and content

OBJECTIVES

The phytoestrogen (plant estrogen) genistein, present in soy products, is of interest because in utero exposure to genistein can cause hypospadias in our mouse model and maternal consumption of soy is prevalent in human populations. Another compound of interest is the fungicide vinclozolin, which also causes hypospadias in the mouse and rat and can occur concurrently with genistein in the diet as a residue on exposed foods. A study in the United Kingdom found no relationship between a maternal organic vegetarian diet and hypospadias frequency, but women who consumed nonorganic vegetarian diets had a greater percentage of sons with hypospadias. Because nonorganic diets can include residues of pesticides such as vinclozolin, we sought to assess the interaction of realistic daily exposures to genistein and vinclozolin and their effects on the incidence of hypospadias.

METHODS

Pregnant mice were fed a soy-free diet and orally gavaged from gestational days 13 to 17 with 0.17 mg/kg/day of genistein, 10 mg/kg/day of vinclozolin, or genistein and vinclozolin together at the same doses, all in 100 μL of corn oil. The controls received the corn oil vehicle. The male fetuses were examined at gestational day 19 for hypospadias, both macroscopically and histologically.

RESULTS

We identified no hypospadias in the corn oil group. The incidence of hypospadias was 25% with genistein alone, 42% with vinclozolin alone, and 41% with genistein and vinclozolin together.

CONCLUSIONS

These findings support the idea that exposure to these compounds during gestation could contribute to the development of hypospadias.

Section snippets

Animals

The committee on animal research at the University of California, San Francisco, approved the scientific protocol. Timed-pregnant CD1 mice (Charles River, Wilmington, Mass) were received on gestational day (GD) 8 and housed in separate animal cages until GD 13. All animals were housed one per cage (20 × 25 × 47 cm) with laboratory-grade pine shavings (heat-treated to remove resins) as bedding. They were acclimated to 20° to 23°F and 40% to 50% relative humidity on a reversed light schedule (14

Results

After macroscopic identification, we analyzed the slide sections histologically. Figure 1 shows sections of genital tubercles from males from each group, including a corn-oil control male (no hypospadias) and males from each treatment group that were identified as having hypospadias. We found that the frequency of hypospadias overall was 0% in the control group (n = 30); 25% in the genistein group (n = 24); 42% in the vinclozolin group (n = 26); and 41% in the combination group (n = 29; Fig. 2).

Comment

Hypospadias is a common congenital abnormality, affecting about 1 in every 250 boys. It is a urethral abnormality in which the urethra opens along the ventral side of the penis, rather than at the tip.8 The final location of the urethral opening and the length of the urethra are androgen-dependent processes that can be disrupted by exposure to antiandrogens8 or estrogens.6 Although reports have suggested that hypospadias has increased in the past few decades,9 these findings remain

Conclusions

Our results indicate that simultaneous maternal consumption of soy and vinclozolin, such as can occur in a nonorganic vegetarian diet, might result in an increase in hypospadias frequency.

References (16)

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