title: The role of androgen-induced growth factor (FGF8) on genital tubercle development in a hypospadiac male rat model of prenatal exposure to di-n-butyl phthalate.
abstract: Fibroblast growth factor 8 (FGF8) is an androgen-induced growth factor (AIGF) that is crucial for embryonic development. This study was developed to investigate the role of FGF8 in developmental abnormalities of the genital tubercle (GT) in hypospadiac male rats when prenatally exposed to di-n-butyl phthalate (DBP). DBP was administered to timed-pregnant rats to establish the hypospadiac rat model where the incidence of hypospadias in male offspring was 43.6%. On postnatal day (PND) 7, decreased mRNA and protein expression levels for androgen receptor (AR) and FGF8 were observed in the GT of hypospadiac rats. Decreased serum testosterone (T) levels were observed in groups displaying hypospadias, which was confirmed using histological analysis. Further anatomical examination using digital photography helped to reveal visualized expression of dysplasia in organs strongly associated with hypospadias. In addition, changes in body weight (BW) and anogenital distance (AGD) were recorded, showing definitive decreases. Collectively, these data clearly demonstrate an interaction between androgen and FGF8, which might play an important role in the occurrence of hypospadias and abnormal organ development induced by DBP.
authors.affiliation: Department of Urology, Shanghai First People's Hospital affiliated to Shanghai Jiaotong University, 85 Wujin road, Shanghai 200080, China.
authors.forename: Shi-Bo
authors.initials: SB
authors.lastname: Liu
authors.affiliation: Department of Urology, Wujiang City No.1 People Hospital affiliated to Nantong University, 169 Gongyuan road, Songling, Wujiang 215200, Jiangsu, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Geriatrics, Shanghai First People's Hospital affiliated to Shanghai Jiaotong University, 85 Wujin road, Shanghai 200080, China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Urology, Shanghai First People's Hospital affiliated to Shanghai Jiaotong University, 85 Wujin road, Shanghai 200080, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Sun
authors.affiliation: Experimental Research Center, Shanghai First People's Hospital affiliated to Shanghai Jiaotong University, 85 Wujin road, Shanghai 200080, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Urology, Jiangsu Province Hospital of Tcm, 155 Hanzhong Road, Nanjing 210029, Jiangsu, China.
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Urology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA; School of Life Sciences, Arizona State University, Tempe, AZ 85285, USA.
authors.forename: Harrison J
authors.initials: HJ
authors.lastname: Stratton
authors.affiliation: Divisions of Neurology and Neurobiology, Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, AZ 85013-4496, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai First People's Hospital affiliated to Shanghai Jiaotong University, 85 Wujin road, Shanghai 200080, China. Electronic address: jjturologist@26.com.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Jiang
mesh_terms: D000818:Animals; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007021:Hypospadias / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D038081:Organogenesis / Q000187:drug effects*; D010413:Penis / Q000002:abnormalities* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity; D013739:Testosterone / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D004785:Environmental Pollutants; C496458:Fgf8 protein, rat; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013723:Teratogens; D051524:Fibroblast Growth Factor 8; D003993:Dibutyl Phthalate; D013739:Testosterone