The Link Between Seminal Cytokine Interleukin 18, Female Circulating Regulatory T Cells, and IVF/ICSI Success

Abstract

Seminal plasma (SP) is thought to be a crucial factor which affects the expansion of regulatory T cells (Tregs) in female reproductive tract during embryo implantation. We propose that seminal transforming growth factor (TGF) β1 is responsible for local accumulation of circulating Tregs, which manifests as changes in Treg frequency in peripheral blood, whereas seminal interleukin (IL) 18 interferes with TGF-β1-dependent cellular reactions. The purpose of the present study is to determine whether the frequency of circulating Tregs is associated with the levels of seminal cytokines and pregnancy establishment in women exposed to partner’s SP during in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle. Twenty-nine women were exposed to SP via timed intercourse before the day of ovum pickup (day-OPU) and also subjected to intravaginal SP application just after OPU. Measurements of seminal TGF-β1 and IL-18 were made by FlowCytomix technology. The percentage of CD4+CD25+CD127low+/ – Tregs among total circulating CD4+ T cells was determined by flow cytometry and the difference between Treg values on the day of embryo transfer and day-OPU was calculated. The percentage of Tregs on the day-OPU, identified as a predictive factor of clinical pregnancy after IVF/ICSI, showed a positive correlation with IL-18 concentration and content of this cytokine per ejaculate ( P < .001 and P < .004, respectively) and negative correlation with the TGF-β1/IL-18 ratio ( P < .014).These findings indicate that the adverse effect of seminal IL-18 excess on implantation may be realized by the prevention of postcoital TGF-β1-related migration of circulating Tregs, which clearly manifests as elevated level of Treg frequency in peripheral blood.

Association of CD200 expression in paternal lymphocytes with female Th1/Th2 balance and pregnancy establishment at immunotherapy of recurrent spontaneous abortion

“…According to modern concepts, the migration of immunocompetent blood cells makes a significant contribution to the formation of a preimplantation immune profile of the endometrium 58. Indeed, in our previous work we have shown that increased frequency of regulatory T cells in female peripheral blood could be the marker of pregnancy failure in IVF/ICSI-treated patients 59. Here, we revealed that increased level of CD200 expression is also associated with an increase in the percentage of regulatory T cells in female peripheral blood in the non-pregnant group (compared with women who became pregnant after LIT).…”