title: Gene expression profile of patients with Mayer-Rokitansky-Küster-Hauser syndrome: new insights into the potential role of developmental pathways.
abstract: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare disease characterized by congenital aplasia of uterus and vagina. Although many studies have investigated several candidate genes, up to now none of them seem to be responsible for the aetiology of the syndrome. In our study, we identified differences in gene expression profile of in vitro cultured vaginal tissue of MRHKS patients using whole-genome microarray analysis. A group of eight out of sixteen MRKHS patients that underwent reconstruction of neovagina with an autologous in vitro cultured vaginal tissue were subjected to microarray analysis and compared with five healthy controls. Results obtained by array were confirmed by qRT-PCR and further extended to other eight MRKHS patients. Gene profiling of MRKHS patients delineated 275 differentially expressed genes, of which 133 downregulated and 142 upregulated. We selected six deregulated genes (MUC1, HOXC8, HOXB2, HOXB5, JAG1 and DLL1) on the basis of their fold change, their differential expression in most patients and their relevant role in embryological development. All patients showed upregulation of MUC1, while HOXB2 and HOXB5 were downregulated, as well as Notch ligands JAG1 and DLL1 in the majority of them. Interestingly, HOXC8 was significantly upregulated in 47% of patients, with a differential expression only in MRKHS type I patients. Taken together, our results highlighted the dysregulation of developmental genes, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract and providing a useful clue for understanding the pathophysiology of MRKHS.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nodale
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ceccarelli
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Giuliano
authors.affiliation: Department of Experimental Medicine, Biotechnology and Molecular Biology Section, Second University of Naples, Naples, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Cammarota
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Sirio
authors.initials: S
authors.lastname: D'Amici
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Vescarelli
authors.affiliation: Department of Gynecologic-Obstetrical and Urologic Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Maffucci
authors.affiliation: Department of Gynecologic-Obstetrical and Urologic Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Bellati
authors.affiliation: Department of Gynecologic-Obstetrical and Urologic Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Pierluigi Benedetti
authors.initials: PB
authors.lastname: Panici
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Romano
authors.affiliation: Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Angeloni
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Marchese
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D000013:Congenital Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D009095:Mullerian Ducts / Q000002:abnormalities* / Q000378:metabolism / Q000601:surgery; D061251:Primary Cell Culture; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014599:Uterus / Q000002:abnormalities / Q000378:metabolism*; D014621:Vagina / Q000002:abnormalities / Q000378:metabolism* / Q000601:surgery
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; C086061:HOXB2 protein, human; C489126:HOXB5 protein, human; C489815:HOXC8 protein, human; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; C060192:MUC1 protein, human; D008565:Membrane Proteins; D018396:Mucin-1; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors