Basic ScienceEndocrine Disruptors and Hypospadias: Role of Genistein and the Fungicide Vinclozolin
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.
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Cited by (59)
Estrogens and development of the mouse and human external genitalia
2021, DifferentiationEndocrine disrupting chemicals in the pathogenesis of hypospadias; developmental and toxicological perspectives
2021, Current Research in ToxicologyCitation Excerpt :Both of these studies highlight the need for further research using improved exposure characterization to confirm an association and define a mechanism of atrazine action. Exposures to antiandrogens such as vinclozolin, a fungicide, also cause hypospadias in both mice (Vilela et al., 2007) and rats (Gray et al., 1999; Kelce et al., 1994). Vinclozolin is regularly used to induce hypospadias in mouse models to investigate the mechanism of antiandrogen action on the development of the urethra (Amato et al., 2018; Yang et al., 2019).
Isolated hypospadias: The impact of prenatal exposure to pesticides, as determined by meconium analysis
2018, Environment InternationalCitation Excerpt :Endocrine-disrupting chemicals (EDCs) may interfere with the normal development of the male external genitalia during early pregnancy (Wang and Baskin, 2008) by altering the endocrine system's normal regulatory functions. Among the many suspected EDCs certain pesticides are known to disrupt the endocrine system in in vitro (Lin and Garry, 2000) and in animal studies (Marouani et al., 2017) including the induction of hypospadias in rats (Vilela et al., 2007). However, no one substance has been formally identified as a risk factor for hypospadias in humans.
Endocrine disrupters: A review
2018, Encyclopedia of Food Chemistry