Abstract
The abortifacient Mifepristone (RU486) has proven to be a safe, effective, acceptable option for millions of women seeking abortion during the first and second trimester of pregnancy although its precise mechanism of action is not well understood. The main objective of this study was to investigate the impact of low dose Mifepristone administration on placental Galectin-9 (Gal-9) expression, as well as its effect on the cell surface expression of Gal-9, TIM-3 and CD107a molecules by different T and NK cell subsets. A model of Mifepristone-induced immunological changes was established in syngeneic pregnant BALB/c mice. RU486-induced alteration in placental Gal-9 expression was determined by immunohistochemistry. For immunophenotypic analysis, mid-pregnancy decidual lymphocytes and peripheral mononuclear cells were obtained from Mifepristone treated and control mice at the 14.5 day of gestation. TIM-3 and Gal-9 expression by peripheral and decidual immune cells were examined by flow cytometry. Our results revealed a dramatically decreased intracellular Gal-9 expression in the spongiotrophoblast layer of the haemochorial placenta in Mifepristone treated pregnant mice. Although low dose RU486 treatment did not cause considerable change in the phenotypic distribution of decidual and peripheral immune cells, it altered the Gal-9 and TIM-3 expression by different NK and T cell subsets. In addition, the treatment significantly decreased the CD107a expression by decidual TIM-3+ NK cells, but increased its expression by decidual NKT cell compared to the peripheral counterparts. These findings suggest that low dose Mifepristone administration might induce immune alterations in both progesterone dependent and independent way.
Highlights
Unintended pregnancy is a major globe tragedy for millions of women representing significant direct and indirect costs to health care, no matter for individuals or society
We examined the alterations of the Gal-9/TIM-3 pathway that might play an important role in the immunological changes caused by Mifepristone treatment
We investigated the percentage of CD4+T, CD8+T, γ/δT, Treg, NK and NKT cells using the lymphocyte gate in the spleen and in the decidua of untreated and RU486 treated pregnant mice
Summary
Unintended pregnancy is a major globe tragedy for millions of women representing significant direct and indirect costs to health care, no matter for individuals or society. The World Health Organization (WHO) estimates that approximately 40–60 million abortions were induced worldwide each year [1]. During the first and second trimester, medical or surgical abortion is one of the oldest, most commonly practiced and most controversial procedure performed worldwide. The immunological effect of Galectin-9/TIM-3 pathway after low dose Mifepristone treatment in pregnant mice
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