The role of HLA-E polymorphism and soluble HLA-E isoform in recurrent reproductive failures and male infertility

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunobiology Pub Date : 2025-11-01 Epub Date: 2025-10-22 DOI:10.1016/j.imbio.2025.153130

Agnieszka Tarnowska , Andrzej Wiśniewski , Julia Burnos , Paweł Radwan , Kazimierz Chorobik , Michał Radwan , Karolina Piekarska , Andrzej Malinowski , Jacek R. Wilczyński , Izabela Nowak

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引用次数: 0

Abstract

Background

Human leukocyte antigen (HLA)-E as a non-classical HLA class I molecule interacting with NK and T cell receptors may activate or inhibit immune responses. These reactions can impact reproductive success because HLA-E is expressed by trophoblast cells. In this study, we investigated rs1264457 A/G HLA-E polymorphism in couples with reproductive failures such as recurrent implantation failure (RIF) after in vitro fertilization (IVF), recurrent spontaneous abortion (RSA), and sporadic spontaneous abortion (SSA) after natural conception. Furthermore, we investigated the role of the soluble HLA-E isoform (sHLA-E) in women's plasma and seminal plasma of men participating in IVF procedures.

Methods

We used real-time PCR with a TaqMan probe to study the rs1264457 polymorphism, which represents a much better-known HLA-E*01:01/HLA-E*01:03 dimorphism, and ELISA test to measure the soluble HLA-E isoform.

Results

Our study indicates that the rs1264457 A/G polymorphism did not influence female infertility or susceptibility to RIF and RSA. However, we noticed that HLA-E*0101 homozygotic men were more susceptible to having severe, very severe oligozoospermia or azoospermia (p = 0.013, OR = 1.70). Moreover, we found a higher concentration of sHLA-E in IVF patients than in control women (p < 0.0001/p_corr. = 0.0024). In turn, a lower level of sHLA-E in semen plasma was associated with fewer sperm cells (p < 0.0001).

Conclusions

HLA-E*0101 homozygosity and lower levels of soluble HLA-E in men's ejaculate are associated with reduced sperm count and may impact male fertility.

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HLA-E多态性和可溶性HLA-E异构体在复发性生殖失败和男性不育中的作用

人类白细胞抗原(HLA)-E作为一种非经典HLA I类分子与NK和T细胞受体相互作用，可激活或抑制免疫反应。这些反应可以影响生殖成功，因为HLA-E是由滋养细胞表达的。在本研究中，我们研究了rs1264457 A/G HLA-E多态性在体外受精（IVF）后复发性着床失败（RIF）、自然受孕后复发性自然流产（RSA）和散发性自然流产（SSA）等生殖失败夫妇中的多态性。此外，我们还研究了可溶性HLA-E异构体（sHLA-E）在参与体外受精程序的女性血浆和男性精浆中的作用。方法采用实时荧光定量PCR和TaqMan探针检测HLA-E*01:01/HLA-E*01:03双态rs1264457多态性，ELISA检测可溶性HLA-E异构体。结果rs1264457 A/G多态性不影响女性不育或对RIF和RSA的易感性。然而，我们注意到HLA-E*0101纯合子男性更容易发生严重、极严重的少精症或无精症（p = 0.013, or = 1.70）。此外，我们发现体外受精患者的sHLA-E浓度高于对照组（p < 0.0001/pcorr）。= 0.0024)。反过来，精液血浆中较低水平的sHLA-E与较少的精子细胞相关（p < 0.0001）。结论男性射精中shla - e *0101纯合性和可溶性HLA-E水平降低与精子数量减少有关，可能影响男性生育能力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunobiology 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

108

审稿时长

55 days

期刊介绍： Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including • Innate Immunity, • Adaptive Immunity, • Complement Biology, • Macrophage and Dendritic Cell Biology, • Parasite Immunology, • Tumour Immunology, • Clinical Immunology, • Immunogenetics, • Immunotherapy and • Immunopathology of infectious, allergic and autoimmune disease.