KIR and HLA-C genes in male infertility

Karolina Wilczyńska,Rafał Krasiński,Michał Radwan,Andrzej Malinowski,Jacek R Wilczyński,Izabela Nowak,Paweł Radwan,Ewa Barcz

doi:10.1007/s10815-020-01814-6

Abstract

PurposeApproximately 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.MethodWe 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.ResultsWe 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.ConclusionFertile men differ in profile of KIR genes and KIR-HLA-C combinations from men participating in IVF.

Highlights

Male factors, either alone or in combination with female causes, contribute to infertility in approximately 50% of couples who fail to conceive
50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we considered whether they differ from fertile males in terms of the frequency of killer immunoglobulin-like receptor (KIR) and HLA-C genes, suggesting the involvement of natural killer (NK) cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis
Comparison of profile of KIR genes in fertile men vs. men participating in in vitro fertilization (IVF) and fertile men vs. recurrent spontaneous abortion

Summary

Introduction

Either alone or in combination with female causes, contribute to infertility in approximately 50% of couples who fail to conceive. This is a growing problem in the world, as well as in Poland. Male infertility can result from anatomical or genetic abnormalities, systemic or neurological diseases, infections, trauma, iatrogenic injury, gonadotoxins, and development of antisperm antibodies. In 30–40% of male infertility cases, no cause is identified, this condition is named: idiopathic male infertility [5]. Male factors may have an influence on fertilization and embryo development failure, an increase in the risk of idiopathic recurrent miscarriages, autosomal dominant diseases, and neurobehavioral disorders in offspring [6]

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Conclusion