Long-term effects of acute cadmium exposure on testis immune privilege

Abstract

Cadmium (Cd) is a widespread and non-biodegradable pollutant of great concern to human health. This element can affect cellular signal transduction and cell-to-cell interaction in the testis. Immune tolerance towards auto- and alloantigens is an important component of testis immunity. It is involved in spermatogenesis and hormone secretion. Plus, the immune tolerance may help to reveal the changes in testis immunity over a long period after Cd exposure. The current research was aimed at investigating the long-term effects of acute Cd exposure on testis immunity by means of elicitation of testicular immune cell composition shift induced by Cd. Cadmium chloride was intraperitoneally injected at 3 mg Cd/kg to mice. After that testis interstitial cells were stained with surface markers for leukocyte and lymphocyte subpopulations (CD45, CD11b, CD3, CD4, CD8, CD25) and analyzed cytofluorimetrically by week 4, 6, 8 and 12 after Cd administration (Cd group). To identify the delayed effects of cadmium on immune tolerance two groups of animals were subjected to intratesticular allotransplantation of neonatal testis (groups ITT and Cd+ ITT). One of the groups was administered with Cd four weeks before the transplantation (Cd+ITT group). I group served as a control that did not undergo any transplantation or Cd injection. For a better demonstration of the phenomenon of immunological tolerance of the testicles, an additional group (UKT group) was used which got grafts under the kidney capsule (non-immune privileged site).Investigation of the cell population showed that CD45+, CD11b+, CD4+, CD8+ cells were permanently present in testicular interstitial tissue in I group. Intratesticular testis transplantation increased the proportion of CD11b+ but did not have such a pronounced effect on CD8+ cells in ITT group. Moreover, the transplantation elevated CD4+ CD25+ cells known for their immunosuppressive property and promoted graft development by week 2 (histological data). Cd injection resulted in severe inflammation that quenched by week 4 (Cd and Cd+ ITT groups). This time point was chosen for transplantation in Cd+ ITT group. Such Cd pretreatment led to a high CD8+ cell proportion and to the delayed appearance of CD4+ CD25+ cells by week 2 (Cd+ ITTgroup). The finding is consistent with the impairment of graft development in Cd+ ITTgroup pretreated with Cd. Observation suggest that Cd pretreatment was associated with disproportion of interstitial immune cell populations which resulted in the impairment of immunoprotective function of the testis. The impairment of testis immunity showed itself only after several weeks of Cd administration, and only when the recipient testis immunity was provoked by alloantigens of donor testes.

Keywords

• cadmium; heavy metal toxicity; immune privilege; male fertility; testis transplantation; t regulatory cells