title: The expression analysis of Bmpr1a and Bmp2 during hindgut development in rat embryos with anorectal malformations.
abstract: The aim of this study was to determine Bmpr1a and Bmp2 expression patterns during anorectal development in normal and anorectal malformation (ARM) embryos with a view to establishing the possible role of Bmpr1a and Bmp2 in ARM pathogenesis. ARM was induced with ethylenethiourea on the 10th gestational day (GD10) in rat embryos. The embryos were harvested by Cesarean deliveries. The expression of Bmpr1a and Bmp2 was evaluated in normal rat embryos (n=213) and ARM embryos (n=236) from GD14 to GD16. Immunohistochemical staining revealed, in normal embryos, that Bmpr1a and Bmp2 was mainly expressed on the epithelium of the urorectal septum (URS) and the cloacal membrane (CM) on GD14 and GD15. When the rectum separated from the urogenital sinus (UGS) on GD16, Bmpr1a- and Bmp2-immunolabeled cells were observed on the anorectal epithelium. In ARM embryos, the epithelium of the hindgut and URS demonstrated faint immunostaining for Bmpr1a and Bmp2. Analyses by Western blot and Real-time PCR revealed that Bmpr1a and Bmp2 protein and mRNA expression were significantly decreased in the ARM hindgut compared with normal hindgut on GD14 and GD15 (P<0.05). In ARM embryos, an imbalance in the spatiotemporal expression of Bmpr1a and Bmp2 was noted during anorectal morphogenesis from GD14 to GD16. Therefore, downregulation of Bmpr1a and Bmp2 at the time of cloacal separation into the primitive rectum and UGS might be related to the development of ARM.
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, PR China.
authors.forename: Xiao Bing
authors.initials: XB
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Women and Children's Hospital of Qingdao City, Qingdao 266034, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, PR China.
authors.forename: Wei Lin
authors.initials: WL
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Health Ministry for Congenital Malformation, Shenyang 110004, PR China.
authors.forename: Zheng Wei
authors.initials: ZW
authors.lastname: Yuan
authors.affiliation: Department of Pediatric Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, PR China. Electronic address: baiyz@sj-hospital.org.
authors.forename: Yu Zuo
authors.initials: YZ
authors.lastname: Bai
mesh_terms: D000818:Animals; D000071056:Anorectal Malformations / Q000235:genetics* / Q000473:pathology; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D004064:Digestive System / Q000196:embryology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger; C498213:Bmpr1a protein, rat; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Anorectal malformation; Bmp2; Bmpr1a; Development; Embryogenesis; Rat