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

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/10 ⁵ 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.
Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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