title: The involvement of inflammatory cytokines in the pathogenesis of recurrent miscarriage.
abstract: OBJECTIVE
  To investigate the inflammatory cytokine expression pattern in trophoblastic tissue from women with unexplained recurrent miscarriage (RM).
  
  
  METHODS
  Trophoblasts were obtained during uterine evacuation from 11 women with RM and from 20 healthy pregnant women undergoing elective termination of pregnancy, who served as controls. The array was performed using GEArray Q Series Human Inflammatory Cytokines & Receptors Gene Array HS-015 membranes. Data were confirmed by quantitative real-time PCR. The Mann-Whitney U test was performed for statistical analysis.
  
  
  RESULTS
  Microarray analysis identified three genes that were differentially expressed between RM patients and controls. We observed significant downregulation of Transforming Growth Factor beta 3 (TGF-β3) and Interleukin 25 (IL-25) (5-fold reduction and 2.5-fold reduction, respectively) and significant upregulation of CD-25, also known as Interleukin 2 receptor alpha (IL-2RA) (7-fold increase) in women with RM compared with controls. The median ΔC(t) of TGF-β3 was 8.2 (interquartile range, 7.67-8.9) in RM patients vs. 5.85 (interquartile range, 5.3-6.09) in controls; the median ΔC(t) of IL-25 was 5.18 (interquartile range, 4.46-5.76) in RM patients vs. 3.85 (interquartile range, 3.6-4.51) in controls, and the median ΔC(t) of CD-25 was 9.62 (interquartile range, 7.81-12.42) in RM patients vs. 12.44 (interquartile range, 11.02-13.86) in controls.
  
  
  CONCLUSIONS
  Our results suggest that the immunological and inflammatory regulation mechanisms of the placental environment play a key role in recurrent miscarriage. The observed trophoblast cytokine expression pattern at the maternal-fetal interface confirms the immunotrophic theory, as demonstrated by a switch from a T-helper-1 (Th1) profile to a T-helper-2 (Th2) profile in women who experience recurrent miscarriages.
authors.affiliation: Department of Clinical Sciences, Section of Woman Health Science, Università Politecnica Marche, Ancona, Italy. s.giannubilo@univpm.it
authors.forename: Stefano R
authors.initials: SR
authors.lastname: Giannubilo
authors.forename: Beatrice
authors.initials: B
authors.lastname: Landi
authors.forename: Valentina
authors.initials: V
authors.lastname: Pozzi
authors.forename: Davide
authors.initials: D
authors.lastname: Sartini
authors.forename: Monia
authors.initials: M
authors.lastname: Cecati
authors.forename: Piergiorgio
authors.initials: P
authors.lastname: Stortoni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corradetti
authors.forename: Franca
authors.initials: F
authors.lastname: Saccucci
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Tranquilli
authors.forename: Monica
authors.initials: M
authors.lastname: Emanuelli
mesh_terms: D000026:Abortion, Habitual / Q000276:immunology*; D000328:Adult; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D011247:Pregnancy; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*; D014327:Trophoblasts / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C486701:IL25 protein, human; C508017:IL2RA protein, human; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D053782:Transforming Growth Factor beta3