Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion

It is widely assumed that, after ovulation, the human endometrium undergoes specific changes and becomes receptive to the implantation of embryo durin g the mid-secretory phase. When implantation does not take place, further c hanges occur which eventually result in the shedding of human endometrium. The present study was carried out to examine whether there are changes in t he cytokine gene expression in human endometrium which are correlated with endometrial function in various phases of the menstrual cycle. The RNase pr otection assay was performed on carefully dated endometria from normal subj ects to characterize the expression of cytokines which potentially contribu te to endometrial function. These included: tumour necrosis factor (TNF), i nterleukin (IL)-1 beta, IL-6, IL-8, leukaemia inhibitory factor (LIF), tran sforming growth factor beta 1 (TGF-beta 1), macrophage colony stimulating f actor (MCSF or colony stimulating factor-1), end vascular endothelial growt h factor (VEGF) mRNAs. A low level of expression of these cytokine mRNAs wa s found during the proliferative and early secretory phase. Expression of c ytokine mRNA increased during the mid-secretory phase and rose to a peak in the late secretory phase. The level of cytokine mRNA expression during ges tation was most akin to that observed during the mid-secretory phase. Indiv iduals with habitual abortion presented with an abnormal expression of IL-1 beta and IL-6 mRNA in endometrium, during the mid-secretory phase. Taken t ogether, these findings are consistent with a progressive rise in the expre ssion of cytokines in human endometrium during the secretory phase in natur al cycles. Furthermore, the findings show that habitual abortion is associa ted with the abnormal expression of IL-1 beta and IL-6 in the mid-secretory phase.