title: Molecular mechanism of Hoxd13-mediated congenital malformations in rat embryos.
abstract: OBJECTIVE
  To investigate the molecular mechanism of Hoxd13-mediated congenital malformations in rat embryos.
  
  
  METHODS
  SD female rats were mated with male rats in a 1:1 mating scheme. Thirty pregnant female rats were randomly divided into three groups: the control group receiving a normal diet, the model group receiving a vitamin A-deficient diet, and the treatment group receiving a vitamin A-deficient diet supplemented with pcDNA-Hoxd13. The expression of Hoxd13 mRNA and protein in normal embryonic tissue and congenital malformations was determined by RT-PCR and Western blot analysis. At day 20, rats were dissected, and the fetal weight, body and tail length, and the number of live births, absorbed fetus, and stillbirth in each group were recorded. Wnt and Slim1 expression was detected by RT-PCR and Western blot analysis. β-catenin and c-myc expression was also quantified by Western blot analysis.
  
  
  RESULTS
  The expression of Hoxd13 mRNA and protein in congenital malformations was significantly lower compared with normal embryonic tissue (P<0.01). The administration of exogenous Hoxd13 in the treatment group markedly increased the fetal weight, body and tail length (P<0.05), improved the embryonic survival rate, and reduced the embryonic resorption rate and stillbirth rate (P<0.05). Exogenous Hoxd13 markedly promoted the expression of Wnt2, Wnt5a, Wnt7b and Slim1 protein and mRNA (P<0.01), and the expression of β-catenin and c-myc protein in congenital malformations (P<0.01).
  
  
  CONCLUSIONS
  Hoxd13 expression was decreased in rat embryos with congenital malformations. The administration of exogenous Hoxd13 alleviated fetal malformation probably through stimulation of Slim1 expression and Wnt/β-catenin signaling pathway.
authors.affiliation: Department of Ultrasonography, Maternal and Children Health Hospital of Tangshan City China.
authors.forename: Fenglan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Ultrasonography, Maternal and Children Health Hospital of Tangshan City China.
authors.forename: Mingzhen
authors.initials: M
authors.lastname: Du
authors.affiliation: Department of Ultrasonography, Maternal and Children Health Hospital of Tangshan City China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Ultrasonography, Maternal and Children Health Hospital of Tangshan City China.
authors.forename: Juekun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Ultrasonography, Maternal and Children Health Hospital of Tangshan City China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Ultrasonography, The Affiliated Hospital of North China University of Science and Technology China.
authors.forename: Huixue
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D020567:Fetal Weight; D005333:Fetus / Q000002:abnormalities / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018014:Gene Transfer Techniques; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D050497:Stillbirth; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000150:complications; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495268:Ctnnb1 protein, rat; C517184:Fhl1 protein, rat; C547057:HOXD13 protein, rat; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D051176:beta Catenin
keywords: Congenital malformations; Hoxd13; Wnt/β-catenin signaling pathway