Abstract

As one of the non-classical major histocompatibility complex(MHC)-1 antigens, Human Leukocyte Antigen G (HLA-G), has been suggested as a prognostic marker to identify the embryo developmental potential. In the present study, we investigated the potential roles of HLA-G in human spermatogenesis and early embryonic development. Quantitative real-time PCR analysis revealed that HLA-G's expression was increased with increased Johnsen score in testicular tissues. There was no significant difference in HLA-G mRNA expression between testicular tissues with Johnsen score of 8–9 and normal sperm from ejaculated semen. HLA-G mRNA expression was detected in human zygotes, embryos and blastocysts but not in unfertilized oocytes. In testicular tissues where sperm was obtained by testicular sperm extraction (Johnsen score was 8 to 9), there were no correlations between HLA-G mRNA expression and fertilization, cleavage and high-quality embryo rates. At 48–72 h post-fertilization, HLA-G expression was higher in fast growing embryos. HLA-G specific siRNA injection into zygotes not only slowed down embryonic cleavage rate at 48 h post-fertilization, but also down-regulated the expression of embryo metabolism related gene (SLC2A1) and cell cycle-regulated gene (CCND2). Taken together, our findings suggested that HLA-G plays significant roles in human spermatogenesis and early embryonic development.

Highlights

  • Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class I antigen characterized by specific tissue distribution and gene variation

  • Except for testicular tissues from azoospermia patients, two testicular tissues retrieved from normospermic patients due to difficulty in semen collection on the day of oocyte retrieval were examined for HLA-G mRNA expression (Fig. 2A and B)

  • Our results demonstrated that HLA-G mRNA levels in testicular tissues with spermatocytes were significantly higher than those with only sertoli cells and/or spermatogonia

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Summary

Introduction

Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex (MHC) class I antigen characterized by specific tissue distribution and gene variation. HLA-G proteins can be expressed as seven distinct isoforms, by means of an alternative splicing from a single primary transcript. Membrane-bound HLA-G can be modified into soluble isoforms [1,2]. As an important immunomodulatory molecule, HLA-G inhibits cytotoxic activity of T cell, natural killer (NK) cell lysis and cell proliferation. HLA-G regulates the maturation, migration, transportation of dendritic cells and cross talk between T cell and NK cell. The functions of HLA-G are fulfilled by inhibitory receptors expressed on the cell surface, such as ILT-2 (immunoglobulin-like transcript2/LILRB1), ILT-4 (Ig-like transcript-4/LILRB2) and KIR2DL4 (killer inhibitory receptor) [4,5,6]. Except for its immune function, the non-immune function of HLA-G in reproduction has been discovered in recent years [2,7,8,9]

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