KIR and HLA-C genes in male infertility

J Assist Reprod Genet. 2020 Aug;37(8):2007-2017. doi: 10.1007/s10815-020-01814-6. Epub 2020 May 20.

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.

Keywords: HLA-C polymorphism; In vitro fertilization embryo transfer; Infertility; KIR; Semen; Sperm quality and recurrent spontaneous abortion.

MeSH terms

  • Abortion, Habitual / genetics
  • Abortion, Habitual / pathology
  • Adult
  • Female
  • Fertilization in Vitro*
  • Gene Frequency
  • Genotype
  • HLA-C Antigens / genetics*
  • Haplotypes / genetics
  • Humans
  • Infertility, Male / genetics*
  • Infertility, Male / pathology
  • Male
  • Pregnancy
  • Receptors, KIR / genetics
  • Receptors, KIR2DL2 / genetics*
  • Receptors, KIR2DL5 / genetics

Substances

  • HLA-C Antigens
  • KIR2DL2 protein, human
  • KIR2DS2 protein, human
  • KIR2DS3 protein, human
  • Receptors, KIR
  • Receptors, KIR2DL2
  • Receptors, KIR2DL5