Abstract

BackgroundEndometriosis (EM) is highly associated with infertility. The precise mechanism underlying EM-associated infertility remains controversial. This study aimed to investigate the pathogenesis of infertility in women with EM by comparing FoxP3+ T regulatory cells (Tregs) expression in the eutopic endometrium of infertile women with EM and endometrium from healthy fertile women.MethodsAs a marker of Tregs, FoxP3 expression was analyzed in eutopic endometrium during the peri-implantation phase in infertile women with mild EM (n = 7), advanced EM (n = 20), and normally fertile women without EM (n = 20). FoxP3 mRNA expression was analyzed by quantitative real-time RT-PCR. FoxP3 protein expression was assessed by immunohistochemistry.ResultsFoxP3 mRNA expression in all infertile patients with EM was significantly higher than the control group (P < 0.05) by non-parametric Mann–Whitney U-test. Further analysis based on the extent of EM revealed that FoxP3 mRNA expression in infertile patients with advanced EM was significantly higher than the mild EM group and the control group (P < 0.05). Immunohistochemistry analysis showed predominant positive staining for FoxP3 protein in the endometrial stroma. In addition, the number of FoxP3+ cells in the eutopic endometrium of infertile women with advanced EM was marginally higher than the mild EM group and the control group, although the differences were not statistically significant (P > 0.05) by two-tailed t-tests.ConclusionsThese findings suggest that FoxP3+ Tregs in the peri-implantation endometrium might participate in the pathogenesis of advanced EM. However, they are not directly involved in the pathogenesis of advanced EM associated with infertility. The differential expression of FoxP3 in infertile women with mild EM and advanced EM implicates that notable differences in the uterine immune status are likely involved in the pathogenesis of mild EM associated with infertility in the peri-implantation endometrium.

Highlights

  • Endometriosis (EM) is highly associated with infertility

  • Patients were divided into two subgroups as follows: 7 patients with mild EM, and 20 with advanced EM

  • Further analysis based on the extent of EM revealed that Forkhead box protein 3 (FoxP3) mRNA expression in infertile patients with advanced EM was significantly higher than the mild EM group and the control group (P < 0.05)

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Summary

Introduction

Endometriosis (EM) is highly associated with infertility. The precise mechanism underlying EM-associated infertility remains controversial. Endometriosis (EM) is a common and benign gynecological disorder that is highly associated with infertility. It affects approximately 10% to 15% of women of reproductive age and 25% to 50% of women with infertility. The mechanisms underlying EM-associated that EM patients have an impaired endometrium and/ or an abnormal endometrial environment which make them functionally unfavorable for implantation and pregnancy progression [2,4]. Forkhead box protein 3 (FoxP3) is a member of the forkhead-box/winged-helix transcription factor family. FoxP3 has been reported to be an essential controlling gene for the development and function of naturally occurring Treg populations

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