title: Expression patterns of the chromosome 21 MicroRNA cluster (miR-99a, miR-125b and let-7c) in chorioamniotic membranes.
abstract: Trisomy 21 (T21) is the most common chromosome abnormality in humans and is associated with a spectrum of phenotypes, including cognitive impairment, congenital heart defects and immune system defects. In addition, T21 is also associated with abnormalities of fetal membranes including chorioamniotic separation, delayed fusion of the chorioamniotic membranes, defects in syncytiotrophoblast formation, as well as amniocyte senescence. There is evidence indicating miRNAs encoded by sequences on chromosome 21 (Chr-21) are involved in several of the cognitive and neurological phenotypes of T21, but the role of Chr-21 derived miRNAs in fetal membrane abnormalities associated with T21 has not been investigated. In the current study, we determined the expression patterns of three miRNAs derived from a cluster on Chr-21 - hsa-miR-99a, hsa-miR-125b and hsa-let-7c in chorioamniotic membranes obtained from term pregnancies with spontaneous rupture (n = 20). Tissue and location specific expression patterns within the chorioamniotic membranes were identified. The rupture zone in the choriodecidua had distinct expression patterns compared to other fetal membrane locations. Despite the increased gene dosage associated with T21, the expression of all three miRNAs was reduced in cultured T21 amniocytes as compared to cultured euploid amniocytes. In silico analysis of experimentally validated targets of the three miRNAs suggest these Chr-21 derived miRNAs play a potential role in fetal membrane rupture and the fetal membrane defects associated with T21.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, United States. Electronic address: modibp@vcu.edu.
authors.forename: Bhavi P
authors.initials: BP
authors.lastname: Modi
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, United States. Electronic address: sonya.washington@vcuhealth.org.
authors.forename: Sonya
authors.initials: S
authors.lastname: Washington
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, United States. Electronic address: scott.walsh@vcuhealth.org.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Walsh
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, United States; Department of Obstetrics and Gynecology, Virginia Commonwealth University, United States; Department of Pathology, Virginia Commonwealth University, United States. Electronic address: colleen.jackson-cook@vcuhealth.org.
authors.forename: Colleen
authors.initials: C
authors.lastname: Jackson-Cook
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, United States. Electronic address: archer.43@osu.edu.
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Archer
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, United States; Department of Obstetrics and Gynecology, Virginia Commonwealth University, United States. Electronic address: jerome.strauss@vcu.health.org.
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000378:metabolism*; D004314:Down Syndrome / Q000235:genetics / Q000378:metabolism*; D005321:Extraembryonic Membranes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism
chemical_list: C531888:MIRN125 microRNA, human; C561679:MIRN99 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Amnion; Choriodecidua; Hsa-let-7c; Hsa-miR-125b; Hsa-miR-99a; Trisomy-21