title: Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.
abstract: This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n-butyl) phthalate (DBP). DBP was administered to timed-pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart-lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen-related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen-related signaling networks might play an important role in the occurrence of ARMs.
authors.affiliation: Department of Urology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 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 Affiliated to Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: En-Hui
authors.initials: EH
authors.lastname: Li
authors.affiliation: Department of Urology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Dong-Liang
authors.initials: DL
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Wen-Lan
authors.initials: WL
authors.lastname: Sun
authors.affiliation: Department of Central Laboratory, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Department of Urology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 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 Affiliated to Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
authors.affiliation: Department of Urology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 100 Haining Road, Shanghai, 200080, China.
authors.forename: Jun-Tao
authors.initials: JT
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000097:blood / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D003993:Dibutyl Phthalate; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D011944:Receptors, Androgen; D003993:Dibutyl Phthalate; D013739:Testosterone
keywords: anorectal malformations; di(n-butyl) phthalate; male rats; neonate; terminal rectum