Seminal plasma induces mRNA expression of IL-1beta, IL-6 and LIF in endometrial epithelial cells in vitro.

Abstract

The influence of seminal plasma on the mRNA expression of cytokines in human endometrial epithelial and stromal cells and the cytokine production of spermatozoa were investigated in vitro. Seminal plasma and spermatozoa were collected from healthy volunteers and were screened by enzyme-linked immunosorbent assay for cytokines. Epithelial and stromal cells from fertile women were cultured on matrigel or polystyrol and incubated with pooled seminal plasma or with transforming growth factor beta1 (TGF-beta1), interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF), which were found to be significantly concentrated in seminal plasma. Endometrial cytokine expression was analysed by RNase protection assay and supported by RT-PCR. Supernatants of highly purified spermatozoa did not contain detectable levels of IL-1beta, IL-6 and VEGF. Screening of seminal plasma revealed concentrations >10-fold above the serum level for TGF-beta1, IL-8 and VEGF. Incubation of epithelial cells with 0.1, 1 and 10% seminal plasma resulted in concentration-dependant stimulation of IL-1beta, IL-6 and LIF mRNA expression. Maximum stimulation was found in epithelial cells from tissue samples taken in the mid secretory phase. Epithelial mRNA expression of IL-1beta, IL-6 and LIF increased by stimulation with TGF-beta1 and IL-8, but not with VEGF. In conclusion, seminal plasma stimulates expression of pro-inflammatory cytokines in endometrial epithelial cells in vitro. This effect might at least in part be exerted by TGF-beta1 and IL-8, abundantly present in seminal plasma. The in-vivo physiological relevance of these in-vitro studies remains to be determined.