Abstract
Interleukin-1 (IL-1) is a regulatory cytokine that plays an important role in the maintenance of the immune environment of the testis, regulation of junction dynamics and cell differentiation during spermatogenesis. Members of the IL-1 family are pleiotropic cytokines that are involved in inflammation, immunoregulation and other homeostatic functions in the body. IL-1α, IL-1β, and the IL-1 receptor antagonistic molecule (IL-1 Ra) are expressed in the testis under normal homeostasis and they further increase upon infection/inflammation. In the present study we have examined the association of Variable Number Tandem Repeats (VNTR) polymorphism of the Interleukin-1 receptor antagonist gene (IL1RN) with human male infertility. The case-control study comprised of two groups: 331 idiopathic infertile patients and 358 fertile healthy men. The study indicates risk of IL1RN2 variant with male infertility (OR: 1.43, CI: 1.1546 to 1.7804, P = 0.001). To our best knowledge, this is the first report that links IL1RN VNTR polymorphism with human male infertility.
Highlights
Testicular homeostasis requires a unique immune status within the male gonad
It was demonstrated that knockout of IL-1 receptor antagonist gene (IL1RN) in mouse affects the normal fertility of males [4]
The genotype and allele frequencies for variable number tandem repeats (VNTR) in the IL1RN gene were compared between controls and different groups of patients (Table 1)
Summary
Testicular homeostasis requires a unique immune status within the male gonad. The immune system acts as a safeguard for immunogenic male germ cells and at the same time permits normal inflammatory response against invading pathogens [1]. Most events of spermatogenesis take place in a unique microenvironment behind the blood-testis barrier (BTB), which is created between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. It was demonstrated that knockout of IL-1 receptor antagonist gene (IL1RN) in mouse affects the normal fertility of males [4]. The variable number tandem repeats (VNTR) polymorphism has been reported within intron 2 of the human IL1RN, consisting of perfect repeats of 86- bp sequence [5]. We hypothesized that VNTR polymorphism of IL1RN gene may influence spermatogenesis and thereby fertility. Based on the biological and pathologic importance of (VNTR) polymorphism of the human IL1RN, it is possible that variations in the IL1RN gene may contribute to the clinical outcomes of male infertility
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