title: Reduced Leydig cell volume and function in adult rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin without a significant effect on spermatogenesis.
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 micrograms/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 micron, 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.
authors.affiliation: Department of Veterinary Anatomy and Public Health, Faculty of Toxicology, College of Veterinary Medicine, Texas A&M University, College Station 77843-4458.
authors.forename: L
authors.initials: L
authors.lastname: Johnson
authors.forename: R
authors.initials: R
authors.lastname: Dickerson
authors.forename: S H
authors.initials: SH
authors.lastname: Safe
authors.forename: C L
authors.initials: CL
authors.lastname: Nyberg
authors.forename: R P
authors.initials: RP
authors.lastname: Lewis
authors.forename: T H
authors.initials: TH
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004822:Epididymis / Q000187:drug effects; D007985:Leydig Cells / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000187:drug effects*; D012669:Seminal Vesicles / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood
chemical_list: D000072317:Polychlorinated Dibenzodioxins; D011944:Receptors, Androgen; D013739:Testosterone