Effect of intrauterine contraceptive devices on cytokine messenger ribonucleic acid expression in the human endometrium

Abstract

To compare cytokine messenger RNA (mRNA) expression in the endometrium exposed to an intrauterine contraceptive device (IUD) and in normal cycling endometrium. Quantitative reverse-transcribed polymerase chain reaction was used to assess interleukin (IL) 1 beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and colony-stimulating factor 1 (CSF-1) mRNA expression in endometrial tissue samples obtained by curettage or at hysterectomy from 11 women using a copper-releasing IUD, 10 women having a levonorgestrel-releasing IUD, and 13 fertile women during different phases of the menstrual cycle. The mRNAs encoding the studied cytokines were detected in all endometrial samples. The mean IL-1 beta, IL-6, and TNF-alpha mRNA levels were higher in the late secretory menstrual phase compared with the proliferative early secretory phase of the menstrual cycle both in endometria exposed to the copper IUD and in the control samples. The IL-1 beta and TNF-alpha mRNA levels were significantly higher in endometria exposed to the copper IUD compared with the control endometria in the late secretory menstrual phase, whereas no difference was found in the expression of these cytokine mRNAs during the proliferative early secretory phase. In contrast, the mean IL-6 mRNA level was higher in the copper IUD-exposed endometria than in the control endometria in the proliferative early secretory but not in the late secretory menstrual phase. In the levonorgestrel IUD-exposed endometria, the mean levels of IL-1 beta, TNF-alpha, and CSF-1 mRNA were similar to those in normal endometrium in the late secretory menstrual phase. The mean IL-6 mRNA level in levonorgestrel IUD-exposed endometria was lower than that in late secretory menstrual phase of controls but, because of a great individual variation in the control samples, the difference did not reach significance. No significant cyclic change nor any difference in relative CSF-1 mRNA levels between the three study groups was detected. These data provide the first evidence that the use of IUDs is associated with alterations in endometrial cytokine expression and that the alterations differ depending on the cytokine and the type of IUD. We speculate that cytokines are involved in intrauterine contraceptive effects of IUDs.