title: Involvement of ITIH5, a candidate gene for congenital uterovaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome), in female genital tract development.
abstract: The ITI (inter-trypsine inhibitor) gene family includes five genes (ITIH1 to ITIH5) that encode proteins involved in the dynamics of the extracellular matrix (ECM). ITIH5 was found inactivated by partial deletion in a case of congenital uterovaginal aplasia, a human rare disease also called Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. The aim of the present study was to analyze the expression of ITIH5 in the uterus in adult life and during embryogenesis in order to establish the involvement of this gene in both normal and pathological conditions of uterus development. This was achieved in mice by reverse transcription-quantitative PCR, whole-mount hybridization, and Western blot analysis. Itih5 expression was much stronger in female genital tract primordia (Müllerian ducts) and derivatives than elsewhere in the body. This gene was strongly expressed during pregnancy and development of the female genital tract, indicating that the encoded protein probably had an important function in the uterus during these periods. Two different specific isoforms of the protein were detected in Müllerian derivatives during embryogenesis and in adults. Although ITIH genes are expected to be predominantly expressed in the liver, ITIH5 is mainly expressed in the uterus during development and adult life. This tends to indicate an additional and specific role of this gene in the female reproductive tract, and furthermore reinforces ITIH5 as a putative candidate gene for MRKH syndrome.
authors.affiliation: CNRS, UMR 6290-IGDR, Rennes, France. karine.morcel@chu-rennes.fr
authors.forename: Karine
authors.initials: K
authors.lastname: Morcel
authors.forename: Tanguy
authors.initials: T
authors.lastname: Watrin
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jaffre
authors.forename: Stéphane
authors.initials: S
authors.lastname: Deschamps
authors.forename: Francis
authors.initials: F
authors.lastname: Omilli
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pellerin
authors.forename: Jean
authors.initials: J
authors.lastname: Levêque
authors.forename: Daniel
authors.initials: D
authors.lastname: Guerrier
mesh_terms: D058489:46, XX Disorders of Sex Development; D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D000013:Congenital Abnormalities; D004195:Disease Models, Animal; D005260:Female; D005836:Genitalia, Female / Q000473:pathology / Q000503:physiopathology*; D017403:In Situ Hybridization; D007668:Kidney / Q000002:abnormalities / Q000473:pathology; D051379:Mice; D009095:Mullerian Ducts / Q000002:abnormalities / Q000473:pathology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019170:Somites / Q000002:abnormalities / Q000473:pathology; D013131:Spine / Q000002:abnormalities / Q000473:pathology; D014599:Uterus / Q000002:abnormalities / Q000473:pathology; D014621:Vagina / Q000002:abnormalities / Q000473:pathology
chemical_list: C580709:ITIH5 protein, mouse; D053491:Proteinase Inhibitory Proteins, Secretory
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