title: Antiphospholipid Antibodies and Infertility: A Gene Expression Study in Decidual Stromal Cells.
abstract: BACKGROUND
  Antiphospholipid antibodies (aPL) have been advocated as potential mediators of unexplained female infertility, but no evidence has yet been raised to support such an association.
  
  
  OBJECTIVE
  To test the hypothesis that aPL might interfere with uterine decidualization, a gene expression study was performed on decidual stromal cells treated with different aPL preparations.
  
  
  METHODS
  Decidual stromal cells were isolated from first-trimester deciduas obtained from two women undergoing elective abortion, and treated with: (i) a β2GPI-dependent aPL monoclonal antibody (IS3); (ii) IS3 plus TIFI, a synthetic peptide mimicking PL-binding region of β2GPI; and (iii) IgG from healthy subjects (NHS). Gene expression data were acquired using human HT-12 v3 beadchip arrays (Illumina). Differential expression analysis was performed by fitting a gene-wise linear model using the treatment group and decidual source as covariates.
  
  
  RESULTS
  In the comparison of IS3 versus IgG NHS-treated decidual cells, gene ontology (GO) enrichment was expressed in terms relating to well-characterized aPL-mediated cellular effects: "inflammatory response," "immune response," "response to stress," "oxydoreductase activity," "metalloendopeptidase activity," and "cytokine/chemokine activity." As expected, almost all genes were up-regulated by IS3 treatment. The same GO categories appeared to be differentially expressed when IS3 treatment was compared to IS3 + TIFI, but with most genes being down-regulated.
  
  
  CONCLUSIONS
  Given the inflammatory response evinced on gene expression analysis of decidual stromal cells treated with a β2GPI -dependent aPL monoclonal antibody, it is feasible that aPL might interfere with uterine decidualization, affecting the early stages of implantation and ultimately resulting in female infertility.
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Chighizola
authors.forename: Francesca
authors.initials: F
authors.lastname: Pregnolato
authors.forename: Elena
authors.initials: E
authors.lastname: Raschi
authors.forename: Claudia
authors.initials: C
authors.lastname: Grossi
authors.forename: Davide
authors.initials: D
authors.lastname: Gentilini
authors.forename: Maria O
authors.initials: MO
authors.lastname: Borghi
authors.forename: Pojen
authors.initials: P
authors.lastname: Chen
authors.forename: Pier L
authors.initials: PL
authors.lastname: Meroni
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000235:genetics*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002478:Cells, Cultured; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D003656:Decidua / Q000276:immunology / Q000473:pathology; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007247:Infertility, Female / Q000235:genetics / Q000276:immunology / Q000628:therapy; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D011247:Pregnancy; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D053482:beta 2-Glycoprotein I / Q000235:genetics / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D003271:Contraceptive Agents, Female; D004967:Estrogens; D007155:Immunologic Factors; D053482:beta 2-Glycoprotein I; D004958:Estradiol; D017258:Medroxyprogesterone Acetate