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Chighizola C.B.,Experimental Laboratory of Immunological and Rheumatologic Researches | Chighizola C.B.,University of Milan | Pregnolato F.,Experimental Laboratory of Immunological and Rheumatologic Researches | Raschi E.,Experimental Laboratory of Immunological and Rheumatologic Researches | And 7 more authors.
Israel Medical Association Journal | Year: 2016

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. Objectives: 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 firsttrimester 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. © 2016, Israel Medical Association. All rights reserved.

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