title: Reduced Fgf10/Fgfr2 and androgen receptor (AR) in anorectal malformations male rats induced by di-n-butyl phthalate (DBP): A study on the local and systemic toxicology of DBP.
abstract: Previous study have demonstrated that not only the anorectal development but also the general conditions of anorectal malformations (ARMs) male rats are severely affected by di-n-butyl phthalate (DBP) maternal exposure. However, the mechanisms underlying DBP-induced congenital defects remain elusive. Reportedly, Fgf10/Fgfr2 and androgen receptor (AR) are pivotal for the development of multiple organs. In this study, we therefore investigated the expression of Fgf10/Fgfr2 together with AR in the terminal rectum and multiple organs of ARM male rats induced by in utero exposure to DBP. DBP was administered to pregnant rats to establish the model and the incidence of ARMs in male offspring was 39.5%. On postnatal day(PND)1, the gross photograph and histopathological staining confirmed the abnormal manifestations in these organs of newborn ARMs. Decreased anogenital distance, body weight and serum testosterone level were observed in ARM male offspring. The reduced expression of Fgf10/Fgfr2 mRNA and protein was seen in terminal rectum and kidney, spleen, liver, heart in ARM male rats, whereas the reduced expression of AR was only observed in the kidney and terminal rectum. Our findings suggest the potential involvement of altered Fgf10/Fgfr2 signaling and AR in pathogenesis of local and systemic development defects in ARMs male rats induce by DBP.
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Jiang
authors.affiliation: Department of Urology Surgery, Linyi People's Hospital, School of Medicine, Taishan Medical College, Linyi, Shangdong, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Xu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
authors.forename: Kristofer
authors.initials: K
authors.lastname: Wood
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 Geriatrics, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Sun
authors.affiliation: First College of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Xu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 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, Shanghai, 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, Shanghai, China. Electronic address: xsjurologist@126.com.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
mesh_terms: D001003:Anal Canal / Q000002:abnormalities* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D001835:Body Weight; D003993:Dibutyl Phthalate / Q000633:toxicity*; D005260:Female; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D012007:Rectum / Q000002:abnormalities* / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood
chemical_list: C496465:Fgf10 protein, rat; D051526:Fibroblast Growth Factor 10; D012333:RNA, Messenger; D011944:Receptors, Androgen; D003993:Dibutyl Phthalate; D013739:Testosterone; C496356:Fgfr2 protein, rat; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Androgen receptor; Anorectal malformations; Di-n-butyl phthalate; Fibroblast growth factor 10; Fibroblast growth factor receptor 2; Multiple organs