The involvement of inflammatory cytokines in the pathogenesis of recurrent miscarriage

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• 作者：Stefano R. Giannubilo^a ; ¹ ; ^{s.giannubilo@univpm.it} ; Beatrice Landi^a ; ¹ ; ^{beatrice.landi@yahoo.it} ; Valentina Pozzi^b ; ^{valentinapozzi81@gmail.com} ; Davide Sartini^b ; ^{davide_sartini@libero.it} ; Monia Cecati^b ; ^{moniacecati@interfree.it} ; Piergiorgio Stortoni^a ; ^{piergiorgiostortoni@hotmail.it} ; Alessandra Corradetti^a ; ^{a_corradetti@libero.it} ; Franca Saccucci^b ; ^{f.saccucci@univpm.it} ; Andrea L. Tranquilli^a ; ^{a.l.tranquilli@univpm.it} ; Monica Emanuelli^b ; ^{m.emanuelli@univpm.it}
• 关键词：Fertility ; Inflammation ; Trophoblast ; PCR array ; Recurrent miscarriage
• 刊名：Cytokine
• 出版年：2012
• 期刊代码：97_10434666
• 类别：imm
• 出版时间：April, 2012
• 卷：58
• 期：1
• 页码：50-56
• 文件大小：550 K

摘要

Objective

To investigate the inflammatory cytokine expression pattern in trophoblastic tissue from women with unexplained recurrent miscarriage (RM).

Study design

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-尾3) 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 螖C_t of TGF-尾3 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 螖C_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 螖C_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.

Discussion

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.