Elsevier

Toxicology

Volume 76, Issue 2, 30 November 1992, Pages 103-118
Toxicology

Reduced Leydig cell volume and function in adult rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin without a significant effect on spermatogenesis

https://doi.org/10.1016/0300-483X(92)90158-BGet rights and content

Abstract

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to alter testicular function. However, its effect on the efficiency of spermatogenesis or on Leydig cell volume has not been determined in adult rats. In two replicas, adult male rats received a single intraperitoneal injection of TCDD at a rate of 0, 12.5, 25.0, or 50.0 μg/kg body weight. Rats were sacrificed 4 weeks after treatment. The cytosolic Ah receptor in the testis was estimated at 10.3 ± 1.2 fmol/mg protein in these adult rats. The presence of the Ah receptor at this concentration in the testis reveals that the testis is a possible target organ for TCDD-induced responses. Left testes were homogenized and testicular spermatids were counted by phase contrast cytometry to determine daily sperm production. Right testes were vascularly perfused with glutaraldehyde, embedded in Epon 812, sectioned at 0.5 μm, stained with toluidine blue and evaluated by stereology for germ cells or Leydig cells. Body weight was reduced (P < 0.01) in a dose-dependent fashion. Testicular weight and daily sperm production per testis were not significantly reduced by TCDD. Androgen receptor concentrations in the testis and prostate were not affected. Weights of two androgen-sensitive organs (seminal vesicles and epididymis) were reduced (P < 0.01) in a dose-dependent fashion and serum concentrations of testosterone were reduced in a dose-dependent fashion in Replica 2. Due to low numbers of animals in Replica 1, the reduced Leydig cell volume was not significant after TCDD treatment; however, in Replica 2 there was a dose-dependent reduction (P < 0.01) in volume per testis of Leydig cell cytoplasm, nuclei, or total Leydig cell volume. Production of testosterone was sufficient to maintain spermatogenesis quantitatively; however, TCDD caused a dose-dependent reduction in Leydig cell function and Leydig cell volume per testis. This study showed for the first time that TCDD-induced androgen deficiency of male rats may be explained by the loss of total volume of Leydig cell cytoplasm. This study also further illustrates the reserve capacity of Leydig cell function to maintain spermatogenesis when the volume of these cells is significantly reduced.

References (47)

  • O.H. Lowry et al.

    Protein measurement with the Folin phenol reagent

    J. Biol. Chem.

    (1951)
  • S. Bandiera et al.

    Competitive binding to the cytosolic 2,3,7,8-TCDD receptor: Effects of structure on the affinities of substituted biphenyls — a QSAR approach

    Biochem. Pharmacol.

    (1983)
  • J.P. van Miller et al.

    Increased incidence of neoplasms in rats exposed to low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Chemosphere

    (1977)
  • E.E. McConnell et al.

    The comparative toxicity of chlorinated dibenzo-p-dioxins in mice and guinea pigs

    Toxicol. Appl. Pharmacol.

    (1978)
  • R.J. Kociba et al.

    2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): Results of a 13-week oral toxicity study in rats

    Toxicol. Appl. Pharmacol.

    (1976)
  • T.A. Gasiewicz et al.

    The effect of total parenteral nutrition on the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat

    Toxicol. Appl. Pharmacol.

    (1980)
  • S. Safe et al.

    PCCDs and PCDFs: Sources and environmental impact

  • A. Poland et al.

    2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity

    Annu. Rev. Pharmacol. Toxicol.

    (1982)
  • J.P. Whitlock

    The regulation of gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin

    Pharmacol. Rev.

    (1987)
  • S.H. Safe

    Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans

    Annu. Rev. Pharmacol. Toxicol.

    (1986)
  • S. Safe et al.

    Mechanism of action

  • J.R. Allen et al.

    Response of chickens to prolonged feeding of crude toxic fat

  • J.M. Kleeman et al.

    Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on testosterone (T) production by isolated perfused testes

    Toxicologist

    (1988)
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