title: Prenatal exposure to di-n-butyl phthalate (DBP) differentially alters androgen cascade in undeformed versus hypospadiac male rat offspring.
abstract: This study was to compare the alterations of androgen cascades in di-n-butyl phthalate (DBP)-exposed male offspring without hypospadias (undeformed) versus those with hypospadias. To induce hypospadias in male offspring, pregnant rats received DBP via oral gavage at a dose of 750mg/kg BW/day during gestational days 14-18. The mRNA expression levels of genes downstream of the androgen signaling pathway, such as androgen receptor (AR) and Srd5a2, in testes of undeformed rat pups were similar to those in controls; in hypospadiac rat pups these levels were significantly lower than those of control pups. In contrast, both undeformed and hypospadiac rats had decreased serum testosterone levels, reduced mRNA expression of key enzymes in the androgen synthetic pathway in the testes, and ablated genes of developmental pathways, such as Shh, Bmp4, Fgf8, Fgf10 and Fgfr2, in the genital tubercle (GT) as compared to those in DBP-unexposed controls, albeit hypospadiac rats had a more severe decrement than those of undeformed rats. Although other possibilities cannot be excluded, our findings suggest that the relatively normal levels of testosterone-AR-Srd5a2 may contribute to the resistance to DBP toxicity in undeformed rats. In conclusion, our results showed a potential correlation between decreased testosterone levels, reduced mRNA expression of AR and Srd5a2 and the occurrence of hypospadias in male rat offspring prenatally exposed to DBP.
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Jiang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Xu
authors.affiliation: Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, 350 W Thomas Rd, Phoenix, AZ 85013, United States.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Wood
authors.affiliation: Department of Geriatrics, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Urology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors.forename: En-Hui
authors.initials: EH
authors.lastname: Li
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China. Electronic address: xsjurologist@126.com.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics; D000818:Animals; D003993:Dibutyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D007021:Hypospadias / Q000097:blood / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014521:Urethra / Q000002:abnormalities
chemical_list: D052244:Endocrine Disruptors; D008565:Membrane Proteins; D010968:Plasticizers; D012333:RNA, Messenger; D011944:Receptors, Androgen; D003993:Dibutyl Phthalate; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548474:Srd5a2 protein, rat
keywords: Androgen cascade; Di-n-butyl phthalate (DBP); Environmental endocrine disrupting compounds (EEDs); Hypospadias; Undeformed rats