Differential expression of the Wnt/ß-catenin pathway in the genital tubercle (GT) of fetal male rat following maternal exposure to di-n-butyl phthalate (DBP).

Di-n-butyl phthalate (DBP) is one of the most abundantly produced endocrine disruptors that leaches out from polyvinyl chloride plastics and can cause hypospadias in male rats during maternal exposure. The objective of this study was to first explore the roles of Wnt/ß-catenin pathway in the fetal rat genital tubercle (GT) following in-utero exposure to DBP. Timed-pregnant rats were given DBP by gastric intubation at a dose of 750 mg/kg body weight (bw)/day from gestation day (GD) 14 to GD18 to establish a rat model of hypospadias. On GD19, genital tubercle down-regulation of ß-catenin, Phospho-GSK-3ß, and up-regulation of GSK-3ß (glycogen synthase kinase-3ß), NFκB in fetal male rats was observed by western blot analysis. ß-catenin was located in the urethral plate epithelium (UPE). Immunochemistry showed that the relative expression of ß-catenin decreased in the DBP-treated fetal rat GT compared to the normal control. These findings, for the first time, indicate that DBP may affect the development of GT by down-regulating the Wnt/ß-catenin pathway in fetal male rats.

[Proteomic analysis of the testis and differential expression of Annexin A3 in hypospadiac rats].

OBJECTIVE: To investigate the effect of in utero exposure to di-n-butyl phthalate (DBP) on the protein expression in the penile tissue of hypospadiac rats, isolate and identify differentially expressed proteins, and determine the role of the differential expression of Annexin A3 in the development of hypospadia in the rat offspring after maternal exposure to DBP. METHODS: Twenty pregnant SD rats were randomly assigned to an experimental group, intragastrically administered DBP at 800 mg/kg, and a control group, given soybean oil at 5 ml/kg, both for 5 days. Three days after birth, the penises of the newborn rats were removed, and the total protein extracted for 2D-electrophoretic separation and image analysis. Differentially expressed protein spots were screened and identified by mass spectrometry, and the changes in the expression of Annexin A3 detected by Western blotting and immunohistochemistry. RESULTS: Thirty-one differentially expressed protein spots were screened, of which 17 were identified by mass spectrometry and the SwissProt database, including pyruvate kinase M2, alpha-enolase, and Annexin A3. Western blot showed that Annexin A3 was mainly located in the urethral epithelia and had a lower expression in the hypospadiac rats (1.851 +/- 0.014, n = 10) than in the controls (2.603 +/- 0.012, n = 10) (P < 0.05). CONCLUSION: A pedigree of differentially expressed proteins in the penises of DBP-induced hypospadia and normal rats was established by the proteomic method. The differential expression of Annexin A3 may play an important role in the development of hypospadia.

TGFbeta1 T29C polymorphism and cancer risk: a meta-analysis based on 40 case-control studies.

Transforming growth factor-beta1 (TGFbeta1) plays a significant role in regulating cellular proliferation and apoptosis. The TGFbeta1 T29C polymorphism reportedly affects cancer risk, but pertinent studies offer conflicting results. We therefore performed a meta-analysis based on 40 studies from 32 publications, assessing the strength of the association using odds ratios with 95% confidence intervals. Overall, no evidence has indicated that individuals carrying CC or CT genotypes had significantly increased cancer risks, compared with TT genotype carriers [CC vs. TT: odds ratio (OR)=1.10, 95% confidence interval (95% CI)=1.00-1.21, P=0.06; CT vs. TT: OR=1.07, 95% CI=0.99-1.16, P=0.09). However, stratified analysis by cancer type and ethnicity indicated a significantly increased risk of prostate cancer (CT vs. TT: OR=1.28, 95% CI=1.01-1.61, P=0.04) and cancer in those of Asian descent (CC vs. TT: OR=1.26, 95% CI=1.03-1.53, P=0.02; CT vs. TT: OR=1.20, 95% CI=1.01-1.43, P=0.04). This association was also observed in the dominant model for prostate cancer. Although not all bias could be eliminated, this meta-analysis suggested that TGFbeta1 29C was a low-penetrant risk factor for prostate cancer and cancer in Asians. A larger single study is still required to evaluate any association with other types of cancer or in other populations.