title: Krüppel-like factor 12 is a novel negative regulator of forkhead box O1 expression: a potential role in impaired decidualization.
abstract: BACKGROUND
  Decidualization is a prerequisite for successful implantation and the establishment of pregnancy. Krüppel-like factor 12 (KLF12) is a negative regulator of endometrial decidualization in vitro. We investigated whether KLF12 was associated with impaired decidualization under conditions of repeated implantation failure (RIF).
  
  
  METHODS
  Uterine tissues were collected from a mouse model of early pregnancy and artificial decidualization for immunohistochemistry, Western blot and real-time PCR analysis. Reporter gene assays, chromatin immunoprecipitation-PCR and avidin-biotin conjugate DNA precipitation assays were performed to analyze the transcriptional regulation of forkhead box O1 (FOXO1) by KLF12. Furthermore, the protein levels of KLF12 and FOXO1 in patients with RIF were analyzed by Western blot and immunohistochemistry.
  
  
  RESULTS
  KLF12 led to defective implantation and decidualization in the mouse uterine model of early pregnancy and artificial decidualization by directly binding to the FOXO1 promoter region and inhibiting its expression in human endometrial stromal cells. Elevated KLF12 expression was accompanied by decreased FOXO1 expression in the endometria of patients with RIF.
  
  
  CONCLUSIONS
  As a novel regulator, KLF12 predominantly controls uterine endometrial differentiation during early pregnancy and leads to implantation failure.
authors.affiliation: Reproductive Medicine Center, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. hellozhanghui@sina.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Science Isotope Laboratory, Nanjing Agricultural University, Nanjing, 210095, Jiangsu, China. xdzhu@njau.edu.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. sun_anjing_87@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. jiangyue85@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. yuanxiao-0223@163.com.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. kongchengcai12@163.com.
authors.forename: Chengcai
authors.initials: C
authors.lastname: Kong
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. xing.jun@msn.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. xmljding@163.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. diaozy1999@tom.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Diao
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. zhenxin_99@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhen
authors.affiliation: Reproductive Medicine Center, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. stevensunz@163.com.
authors.forename: Haixiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medicine Center, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, 210008, Jiangsu, China. yanguijun55@163.com.
authors.forename: Guijun
authors.initials: G
authors.lastname: Yan
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003656:Decidua / Q000378:metabolism*; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors