Abstract

Clinically, immune cell function is correlated with pathogenesis of endometrial polyp (EP) and infertility of women of reproductive-age. However, the underlying immune cell hallmark in EP patients remains unclear. Here, we focused on analyzing circulating immune cells, and attempted to reveal the correlation between peripheral immune cell functional phenotypes and fertility in EP patients. Through comparison of circulating CD4+/CD8+ T cells, NK cells, and γδ T cells between 64 EP patients and 68 healthy females, we found that γδ T cells, but not CD4+/CD8+ T cells and NK cells, were immunologically correlated with conception rate and conception interval time. Specifically, total γδ T cells and the Vδ1+PD1+ γδ T subpopulation decreased whereas the Vδ1/Vδ2 ratio increased in EP patients compared to healthy controls. Moreover, the patients with the higher Vδ1/Vδ2 ratio (median value equals 1.04) had a poorer fertility and longer interval time of conception (210 days versus 158 days for control). Meanwhile, higher Vδ1+PD1+ γδ T cell proportion (median equals 15.7) was positively correlative with both higher conception rate and shortened median conception interval time (130 days for Vδ1+PD1high group versus 194 days for Vδ1+PD1low group). Notably, in healthy controls, both Vδ1/Vδ2 ratio and Vδ1+PD1+ γδ T cell proportion correlated with pregnancy rate oppositely, comparing to EP patients. Together, our results suggested that imbalanced γδ T cell population occurred in EP patients, and that Vδ1/Vδ2 ratio and PD-1 expression of Vδ1+ γδ T cells could be potentially developed into valuable predictors for fertility in EP patients.

Highlights

  • The dynamic equilibrium is one type of fundamental features of human endometrium, for example, rebalancing between periodical proliferation and apoptosis, tissue breakdown, and repairment, which serves the major and basic function of regulating embryo implantation [1]

  • We focused on functional phenotype alterations of circulating immune cells (CD4+/CD8+ T cells, natural killer (NK), and gd T cells) in endometrial polyp (EP) patients, and aimed to discover immune cell related biomarkers associating with pregnancy ability

  • Previous study showed that various immune cells, including natural killer (NK) cells [17], macrophages [9], and CD4+ T cells [18], play key roles in maintaining normal pregnancy at term, how peripheral immunity affects pregnancy ability is yet to be fully understood

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Summary

Introduction

The dynamic equilibrium is one type of fundamental features of human endometrium, for example, rebalancing between periodical proliferation and apoptosis, tissue breakdown, and repairment, which serves the major and basic function of regulating embryo implantation [1]. The excessive proliferation of endometrium would occur in certain condition of inductions, and this could adversely. Endometrial polyp (EP) is one consequence of excessive proliferation of endometrium commonly occurring in women of reproductive-age. EP is a type of benign lesion in women with focal growth of the endometrial glands and stroma [2]. EP affects approximately 7.8– 34.9% of reproductive women and usually impairs fertility [3, 4]. In addition to fertility impairment, abnormal uterine bleeding (AUB) is another common symptom of EP, which relates to aberrant tissue damage and repair in endometrium. It generally recognized that EP can negatively affect the quality of life, such as physical, emotional, sexual, and professional aspects of the lives of women [7]

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