Reduced expression of IL-6 and IL-1α mRNAs in secretory phase endometrium of women with recurrent miscarriage

A diverse array of cytokines is implicated in regulating the immune adaptation and endometrial tissue remodelling events that facilitate successful embryo implantation and early placental development. The aim of this study was to evaluate expression of mRNAs encoding a panel of immunoregulatory cytokines in the endometrium of fertile women and women experiencing recurrent miscarriage using highly sensitive, quantitative RT-PCR assays. Endometrial biopsies were collected during the mid-secretory phase of the menstrual cycle from women classified as proven fertile (control; n=12) and women experiencing unexplained recurrent miscarriage (RM; n=9). Reduced IL-6 mRNA and reduced IL-1alpha mRNA were independently associated with recurrent miscarriage. Altered expression was evident after accounting for variation in the composition of endometrial biopsies by normalization of data to epithelial and mesenchymal cell-specific transcripts, cytokeratin-18 mRNA and vimentin mRNA, respectively. The relative abundance of mRNAs encoding LIF, GM-CSF, IFNgamma, IL-1beta, IL-4, IL-5, IL-10, IL-12p40, TNFalpha, TGFbeta1, TGFbeta2 and TGFbeta3 were not altered in recurrent miscarriage tissue. Associations between expression of IL-10, LIF, GM-CSF and TGFbeta2 suggest that regulatory circuits link the transcription of these cytokine genes. Inadequate expression of IL-6 and IL-1alpha mRNAs in endometrial tissue may predispose to recurrent miscarriage through a perturbed maternal immune response, effects on decidual tissue remodeling and angiogenesis, or dysregulated trophoblast differentiation and invasion. Quantitative RT-PCR assays for these cytokines in endometrial biopsies may be a realistic strategy for development of novel diagnostics for predisposition to recurrent miscarriage.