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

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.

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.

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).

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.