Seminal antibodies to human 60kd heat shock protein (HSP 60) in male partners of subfertile couples

Abstract

Background: Heat shock proteins (HSP) are essential mammalian and bacterial stress proteins. At the cellular level, they act as chaperones, have important regulatory functions, and are considered to be an essential factor for reproduction. Scarce information exists on the role of sensitization to HSP and the potential role in the aetiology of male infertility. Methods: The potential association of immunoglobulin (Ig)A antibodies (Ab) to the human 60 kDa heat shock protein (HSP 60) with several parameters of subclinical male genital tract infection/inflammation and with semen quality and sperm fertilizing capacity was analysed in a prospective study. IgA Ab to human HSP 60 were determined in seminal plasma of 202 randomly chosen male partners of subfertile couples with a median duration of infertility of 4 years (range 1-15 years), who were asymptomatic for genital tract infection. After medical history and clinical examination, a comprehensive evaluation of semen quality, in aliquots of the same ejaculates used for HSP Ab determination, included: sperm analysis; local antisperm antibody (ASA) screening; standardized sperm-cervical mucus (CM) penetration testing; immunocytochemical round cell differentiation to determine seminal leukocyte counts; evaluation of complement fraction C3 and of some pro-inflammatory cytokines; and microbial screening. Subsequent fertility was recorded after 6 months. Results: The presence of HSP 60 IgA Ab in seminal fluid (total positive 6.9%) was significantly associated with leukocytospermia, the presence of C3, and also with high interleukin (IL) levels in seminal plasma. HSP 60 Ab were not related to the bacterial colonization of ejaculates. There was no association of seminal IgA Ab to human HSP 60 with semen quality, determined with microscopical semen analysis, nor with local IgG- or IgA-class ASA. There was no relationship with sperm intrinsic motility and duration of motility in the sperm CM-penetration test, nor with sperm fertilizing capacity. Conclusions: The combined presence of IgA Ab to human 60 kDa HSP, leukocytes and other established infection/inflammation markers in semen might suggest a potential role of the immune response to heat shock proteins (HSP) in cases of silent male genital tract infection, but the results do not indicate a marked relationship of HSP 60 Ab in seminal fluid with standard parameters of semen quality.