title: Proteomics of the human endometrial glandular epithelium and stroma from the proliferative and secretory phases of the menstrual cycle.
abstract: Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Hood
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan Harbin Medical University, Harbin, China.
authors.forename: Baoquan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia.
authors.forename: Addie
authors.initials: A
authors.lastname: Alkhas
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Rusheeswar
authors.initials: R
authors.lastname: Challa
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia.
authors.forename: Guisong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Susan
authors.initials: S
authors.lastname: Ferguson
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia.
authors.forename: Julie
authors.initials: J
authors.lastname: Oliver
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia.
authors.forename: Dave
authors.initials: D
authors.lastname: Mitchell
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Bateman
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Zahn
authors.affiliation: Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, Virginia.
authors.forename: Mark
authors.initials: M
authors.lastname: Payson
authors.affiliation: Greenville Hospital System, University of South Carolina School of Medicine, Greenville, Greenville, South Carolina.
authors.forename: Bruce
authors.initials: B
authors.lastname: Lessey
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan.
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia Department of Obstetrics and Gynecology, Inova Fairfax Hospital, Falls Church, Virginia.
authors.forename: G Larry
authors.initials: GL
authors.lastname: Maxwell
authors.affiliation: Women's Health Integrated Research Center at Inova Health System, Annandale, Virginia conrads@whirc.org.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Conrads
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan john.risinger@hc.msu.edu.
authors.forename: John I
authors.initials: JI
authors.lastname: Risinger
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004717:Endometrium / Q000166:cytology*; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D005498:Follicular Phase / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008183:Luteal Phase / Q000502:physiology*; D042282:Microdissection; D010215:Papio; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D011755:Pyrophosphatases / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014599:Uterus / Q000166:cytology
chemical_list: C427944:ENPP3 protein, human; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases
keywords: ENPP3; menstrual cycle; proliferative; proteomics; secretory