Effects on the Local Immunity in the Testis by Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) in Mice

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  • KITAOKA Miyuki
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
  • HIRAI Shuichi
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
  • TERAYAMA Hayato
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
  • NAITO Munekazu
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
  • QU Ning
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
  • HATAYAMA Naoyuki
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
  • MIYASO Hidenobu
    Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
  • MATSUNO Yoshiharu
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
  • KOMIYAMA Masatoshi
    Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
  • ITOH Masahiro
    Department of Anatomy, Tokyo Medical University, Tokyo 160-8402, Japan
  • MORI Chisato
    Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

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Exposure to di-(2-ethylhexyl) phthalate (DEHP) has been reported to induce spermatogenic disturbance through oxidant stress and affect the immune system as an adjuvant. However, the effect of DEHP on the testicular immune microenvironment has not yet been investigated. In the present study, we examined the testicular immune microenvironment after exposure to doses of DEHP, previously identified as no-observed-adverse-effect levels. Adult male mice were administered food containing 0%, 0.01% or 0.1% DEHP and then testes were analyzed. The results showed that a slight but significant spermatogenic disturbance appeared in the 0.1% DEHP group but not in the 0.01% DEHP group at 8 weeks. It was also demonstrated that lymphocytes and F4/80- and MHC class II- positive cells were significantly increased with the elevation of IL-10 and IFN-γ mRNA expressions in the testes of not only the 0.1% DEHP group but also the 0.01% DEHP group at 8 weeks. Histochemical analyses involving horseradish peroxidase (HRP) as a tracer showed that a little blood-borne HRP had infiltrated into the lumen of a few seminiferous tubules beyond the blood-testis-barrier in both the 0.1% and 0.01% DEHP groups at 8 weeks. This indicates that a dose of DEHP that has little effects on spermatogenesis can change the testicular immune microenvironment with functional damage of the blood-testis barrier.

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