Differential expression of ATF3 in male rats with hypospadias induced by combination of Di-n-butyl phthalate and glucocorticoids

Abstract

Objective To verify the differential expression of ATF3 in the genital tubercle (GT) of rats with hypospadias induced by maternal exposure to Di-n-butyl phthalate (DBP) or DBP + dexamethasone (DXM) in order to further explore the mechanism of hypospadias. Methods Forty pregnant SD rats were randomly divided into four groups which were given: group A, soybean oil oral gavage 2 ml/day;DBP (700 mg/kg gavage) + DXM (0. 1 mg/kg sc-injection) during gestational day (GD) 14-18. Pregnant rats were killed at GD 19, birth weight (BW) and anogenital distance (AGD) were recorded in the fetal rats, GT was harvested to verify the expression of ATF3 by Western blotting and immunohistochemistry. Results DXM alone had no effect except to reduce BW but could increase the teratogenic effect of DBP when combined with DBO. The BW and AGD/BW in group D were significantly lower than in group C. The expression of ATF3 had statisticall significant difference between groups C or D and group A, as well as between groups C and D (P ＜ 0. 05). ATF3 was mainly located in the urethral epithelium and mesenchyme. Conclusion These results suggests that exposure to common environmental chemicals in combination with environmental endocrine disrupters may increase the risk of male reproductive abnormalities,such as hypospadias. Up-regulation of ATF3 may affect urethral fold fusion, and then lead to the occurrence of hypospadias. Key words: ATF3; Glucocorticoids; Di-n-butyl phthalate; Hypospadias