title: Critical role for TWIST1 in the induction of human uterine decidualization.
abstract: The importance of the transcription factor TWIST1 for uterine decidualization was examined in human uterine fibroblast (HUF) cells decidualized in vitro with medroxyprogesterone, estradiol (E2), and prostaglandin E2. TWIST1 mRNA levels increased by 6.0- to 6.8-fold during the first 1-2 d of decidualization and remained above predecidualization levels for up to 15 d. Pretreatment of HUF cells with a TWIST1 small interfering RNA (siRNA) for 3 d before the induction of decidualization resulted in less morphologic differentiation than HUF cells pretreated with a nonsilencing control RNA. In addition, the cells pretreated with TWIST1 siRNA expressed 75-95% less IGF binding protein 1, LEFTY2, fibromodulin, laminin, and several other mRNA during decidualization, including the mRNA for the transcription factors forkhead box protein O1 and v-ets-erythroblastosis virus E26, both of which were previously shown to be critical for the induction of decidualization. The HUF cells pretreated with the TWIST1 siRNA also underwent less apoptosis during decidualization than the control cells, as evidenced by a 20% decrease in DNA fragmentation (terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling assay) and a 43-48% decrease in caspase 3, BCL2-associated X protein, and TNF receptor superfamily member 6 mRNA levels. Although the knockdown of TWIST1 expression markedly attenuated the induction of decidualization, overexpression of TWIST1 alone was insufficient to induce the decidualization of HUF cells. Taken together, these findings strongly implicate an essential role for TWIST1 in the initiation of human decidualization and uterine stromal cell apoptosis that occurs upstream of the induction of forkhead box protein O1 and v-ets-erythroblastosis virus E26 mRNA.
authors.affiliation: Department of Pediatrics, University of Cincinnati and Division of Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229-3039, USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Schroeder
authors.forename: Cherie A
authors.initials: CA
authors.lastname: Kessler
authors.forename: Stuart
authors.initials: S
authors.lastname: Handwerger
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008525:Medroxyprogesterone / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C494041:ETS1 protein, human; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D004958:Estradiol; D008525:Medroxyprogesterone; D015232:Dinoprostone