title: Transcriptional Profiling of Human Endocervical Tissues Reveals Distinct Gene Expression in the Follicular and Luteal Phases of the Menstrual Cycle.
abstract: The endocervix plays an important role in providing appropriate protective mechanisms of the upper female reproductive tract (FRT) while at the same time providing the appropriate milieu for sperm transport. Hormone fluctuations throughout the menstrual cycle contribute to changes in the mucosal environment that render the FRT vulnerable to infectious diseases. The objective of this study was to identify genes in human endocervix tissues that were differentially expressed in the follicular versus the luteal phases of the menstrual cycle using gene expression profiling. A microarray using the IIlumina platform was performed with eight endocervix tissues from follicular and four tissues from luteal phases of the menstrual cycle. Data analysis revealed significant differential expression of 110 genes between the two phases, with a P value <0.05 and a fold change cutoff of 1.5. Categorization of these genes, using Ingenuity Pathway Analysis, MetaCore from Thomson Reuters, and DAVID, revealed genes associated with extracellular matrix remodeling and cell-matrix interactions, amino acid metabolism, and lipid metabolism, as well as immune regulation in the follicular phase tissues. In luteal phase tissues, genes associated with chromatin remodeling, inflammation, angiogenesis, oxidative stress, and immune cell regulation were predominately expressed. Using samples from additional patients' tissues, select genes were confirmed by quantitative real-time PCR; immunohistochemical staining was also done to examine protein levels. This is the first microarray analysis comparing gene expression in endocervix tissues in cycling women. This study identified key genes and molecular pathways that were differentially regulated during the menstrual cycle.
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Sevim
authors.initials: S
authors.lastname: Yildiz-Arslan
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: John S
authors.initials: JS
authors.lastname: Coon
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.affiliation: Division of Reproductive Science in Medicine, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois j-kim4@northwestern.edu.
authors.forename: J Julie
authors.initials: JJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D002584:Cervix Uteri / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D005498:Follicular Phase / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D008183:Luteal Phase / Q000378:metabolism*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction
keywords: endocervix; follicular; luteal; menstrual cycle