Dataset Information

KIR and HLA-C genes in male infertility.

ABSTRACT: PURPOSE:Approximately 50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we therefore considered whether they differ from fertile males in terms of the frequency of KIR and HLA-C genes, suggesting the involvement of NK cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis. METHOD:We tested a total of 1064 men: 445 of them were patients who, together with their female partners, participated in in vitro fertilization (IVF), 298 men whose female partners suffered from recurrent spontaneous abortion. Three hundred twenty-one fertile men constituted the control group. KIRs were genotyped using KIR Ready Gene kits and HLA-C by PCR-SSP methods. RESULTS:We found differences in KIR gene frequencies between men who became fathers via natural conception and men who participated in in vitro fertilization for KIR2DL2 (p/pcorr.?=?0.0015/0.035, OR?=?1.61), KIR2DL5 gr.2 (p/pcorr.?=?0.0023/0.05, OR?=?1.64), KIR2DS2 (p/pcorr.?=?0.0019/0.044, OR?=?1.59), and KIR2DS3 (p/pcorr.?=?0.0016/0.037, OR?=?1.67). KIRs in Cen AA region were significantly overrepresented in fertile males than in IVF males (p/pcorr.?=?0.0076/0.03, OR?=?0.67), whereas Cen AB + Cen BB frequency was higher in IVF males than in fertile males (p/pcorr.?=?0.0076/0.03, OR?=?1.50). We also observed a limited association in KIR-HLA-C combinations. CONCLUSION:Fertile men differ in profile of KIR genes and KIR-HLA-C combinations from men participating in IVF.

SUBMITTER: Wilczynska K

PROVIDER: S-EPMC7467998 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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KIR and HLA-C genes in male infertility.

Wilczyńska Karolina K Radwan Paweł P Krasiński Rafał R Radwan Michał M Wilczyński Jacek R JR Malinowski Andrzej A Barcz Ewa E Nowak Izabela I

Journal of assisted reproduction and genetics 20200520 8

<h4>Purpose</h4>Approximately 50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we therefore considered whether they differ from fertile males in terms of the frequency of KIR and HLA-C genes, suggesting the involvement of NK cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis.<h4>Method</h4>We tested a total of 1064 men: 445 of them were patients who, together with their female partners, participat ...[more]

PMID: 32436047

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Project description:Successful reproduction depends on many factors. Male factors contribute to infertility in approximately 50% of couples who fail to conceive. Seminal plasma consists of secretions from different accessory glands containing a mixture of various cytokines, chemokines, and growth factors, which together can induce a local immune response that might impact on a male's as well as a female's fertility. Human leukocyte antigen (HLA)-G expression has been suggested as an immunomodulatory molecule that influences pregnancy outcome. The HLA-G gene encodes either membrane-bound or/and soluble proteins. The aim of this study was the evaluation of HLA-G polymorphisms and their impact on soluble HLA-G (sHLA-G) production. We tested the HLA-G polymorphism in three positions: rs1632947: c.-964G>A; rs1233334: c.-725G>C/T in the promoter region; rs371194629: c.∗65_∗66insATTTGTTCATGCCT in the 3' untranslated region. We tested two cohorts of men: 663 who participated in in vitro fertilization (test material was blood or sperm), and 320 fertile controls who possessed children born after natural conception (test material was blood). Since 50% of men visiting assisted reproductive clinics have abnormal semen parameters, we wondered if men with normal sperm parameters differ from those with abnormal parameters in terms of HLA-G polymorphism and secretion of sHLA-G into semen. We found that certain rs1632947-rs1233334-rs371194629 HLA-G haplotypes and diplotypes were associated with male infertility, while others were protective. Normozoospermic men with the A-C-del haplotype and A-C-del/A-C-del diplotype secreted the most sHLA-G into semen (574.1 IU/mL and 1047.0 IU/mL, respectively), while those with the G-C-ins haplotype and G-C-ins/G-C-ins diplotype - the least (80.8 IU/mL and 75.7 IU/mL, respectively). Men with the remaining haplotypes/diplotypes secreted sHLA-G at an intermediate level. However, only in one haplotype, namely G-C-ins, did we observe strong significant differences in the concentration of sHLA-G in the semen of men with teratozoospermia compared to men with normal sperm parameters (p = 0.009). In conclusion, fertile men differ in the profile of HLA-G polymorphism from men participating in IVF. Among all HLA-G haplotypes, the most unfavorable for male fertility is the G-C-ins haplotype, which determines the secretion of the lowest concentration of the soluble HLA-G molecule. This haplotype may reduce sperm parameters.

Dataset Information

KIR and HLA-C genes in male infertility.

Publications

KIR and HLA-C genes in male infertility.

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