Pathogenic consequences in semen quality of an autoimmune response against the prostate gland: from animal models to human disease

J Immunol. 2006 Jul 15;177(2):957-67. doi: 10.4049/jimmunol.177.2.957.

Abstract

We have recently proposed an autoimmune etiology in approximately 35% of chronic nonbacterial prostatitis patients, the most frequent form of prostatitis observed, because they exhibit IFN-gamma-secreting lymphocytes specific to prostate Ags. Interestingly, this particular group of patients, but not the rest of chronic nonbacterial prostatitis patients, also presented striking abnormalities in their semen quality. In this work, we use an experimental animal model of autoimmune prostatitis on Wistar rats developed in our laboratory to investigate when, where, and how sperm cells from autoimmune prostatitis individuals are being damaged. As in patients, a marked reduction in sperm concentration, almost null sperm motility and viability, and an increased percentage of apoptotic spermatozoa were detected in samples from animals with the disease. Prostate-specific autoantibodies as well as elevated levels of NO, TNF-alpha, and IFN-gamma were also detected in their seminal plasma. In contrast, epididymal spermatozoa remain intact, indicating that sperm damage occurs at the moment of joining of prostate secretion to sperm cells during ejaculation. These results were further supported by experiments in which mixture of normal sperm cells with autoimmune seminal plasma were performed. We hypothesize that sperm damage in experimental autoimmune prostatitis can be the consequence of an inflammatory milieu, originally produced by an autoimmune response in the prostate; a diminished prostate functionality, evidenced by reduced levels of citric acid in semen or by both mechanisms simultaneously. Once more, we suggest that autoimmunity to prostate may have consequences on fertility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology*
  • Biomarkers / metabolism
  • Citric Acid / antagonists & inhibitors
  • Citric Acid / metabolism
  • Cytokines / biosynthesis
  • Cytokines / physiology
  • Disease Models, Animal
  • Down-Regulation
  • Humans
  • Interferon-gamma / biosynthesis
  • Male
  • Nitric Oxide / biosynthesis
  • Prostate / immunology
  • Prostate / pathology*
  • Prostatitis / immunology*
  • Prostatitis / metabolism
  • Prostatitis / pathology*
  • Rats
  • Rats, Wistar
  • Semen / immunology*
  • Semen / metabolism
  • Sperm Capacitation / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Biomarkers
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Citric Acid
  • Nitric Oxide
  • Interferon-gamma