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

Purpose: 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 rs1264457 polymorphism 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 prone to have 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).

Conclusion: sHLA-E isoform in men is associated with semen parameters, especially with the number of sperm cells in ejaculate.