Decreased ratio of FOXP3+/FOXP3-CD45RA+CD4+ T cells in peripheral blood is associated with unexplained infertility and ART failure

Abstract

Unexplained infertility has a huge social impact and is a significant challenge for both clinicians and researchers. Previous studies have shown the involvement of multiple factors in infertility. Among these, the subset of regulatory T cells is of particular interest for the maternal tolerance towards the semi-allogenic fetus. We investigated circulating CD45RA⁺ regulatory and non-regulatory CD4⁺ T cells in healthy women and patients with unexplained infertility in the context of thymic output and peripheral proliferation. The proportion of FOXP3⁺ and FOXP3^-CD45RA⁺CD4⁺ T cells in peripheral blood was studied in control groups of healthy parous and nulliparous (never-pregnant) women and in patients with unexplained infertility. In the same groups thymic output and peripheral proliferation were defined by the sj/βTREC ratio, and signal joint T-cell receptor excision circles (sjTREC) and Ki67 expression, respectively. In parous women a decrease in sjTREC/10⁵ cells and CD45RA⁺ T lymphocytes, compared to nulliparous group was found. At the same time, the proportion of FOXP3^-CD45RA⁺CD4⁺ cells, but not FOXP3⁺CD45RA⁺ Tregs was reduced. In contrast, in patients with unsuccessful pregnancy, proportions of both regulatory and non-regulatory T cell counterparts were lower. Taken together, our results provide evidence for group-specific properties in the CD45RA⁺ T cell compartment between healthy parous, nulliparous and women with unexplained infertility.

Keywords: CD45RA(+) T cells; Infertility; Pregnancy; Regulatory T cells; T-cell receptor excision circle.