Cadmium exposure increases susceptibility to testicular autoimmunity in mice

J Appl Toxicol. 2013 Jul;33(7):652-60. doi: 10.1002/jat.2713. Epub 2012 Jan 23.

Abstract

Cadmium, one of various environmental toxicants, is known to suppress systemic immunity and to injure the testicular capillary endothelia with resultant necrosis of testicular tissues in mice and rats treated with high doses. Recently, it also became evident that cadmium can affect the integrity of the blood-testis barrier (BTB), the endocrine function of Leydig cells, apoptosis of germ cells and systemic immunity, even on treatment with a low dose that does not induce spermatogenic disturbance. Experimental autoimmune orchitis (EAO), i.e., an organ-specific autoimmunity of the testis, can be induced by repeated immunization with testicular antigens, and its pathology is characterized by lymphocytic inflammation and spermatogenic disturbance. In the present study, we investigated the morphological and functional changes of testes in mice treated with a low dose of cadmium chloride (CdCl2 ) and also examined its toxicity as to susceptibility to EAO. The results showed that exposure to 3 mg CdCl2 kg(-1) body weight did not affect the spermatogenic state. However, the BTB at the tubuli recti and the rete testis, but not the seminiferous tubules, was slightly weakened, and intra-testicular mRNA expression of interleukin (IL)-6, tumor necrosis factor-α and IL-1β was significantly increased by the CdCl2 treatment. Furthermore, immunization with testicular antigens after the CdCl2 exposure significantly augmented the EAO severity. Therefore, exposure to a low dose of CdCl2 induces no significant disturbance of spermatogenesis, however, it does change the immunological microcircumstances in the testis, resulting in increased susceptibility to testicular autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / immunology*
  • Blood-Testis Barrier / drug effects
  • Cadmium Chloride / pharmacokinetics
  • Cadmium Chloride / toxicity*
  • Cytokines / biosynthesis
  • Cytokines / isolation & purification
  • Environmental Pollutants / toxicity*
  • Horseradish Peroxidase
  • Kidney / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Orchitis / chemically induced
  • Orchitis / immunology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Testicular Diseases / chemically induced*
  • Testicular Diseases / immunology*
  • Testis / drug effects
  • Testis / immunology
  • Testis / metabolism

Substances

  • Cytokines
  • Environmental Pollutants
  • RNA, Messenger
  • Horseradish Peroxidase
  • Cadmium Chloride