Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells.
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters testicular steroidogenesis and reduces total Leydig cell volume in the testis. However, its effect on Leydig cell number, size, and organelle content had not been determined in adult rats. Adult male rats received a single intraperitoneal injection of TCDD at a dose of 0, 12.5, 25.0, or 50.0 micrograms/kg body weight. Testicular tissues were obtained from rats 4 weeks after treatment. Testes were vascularly perfused with glutaraldehyde, embedded in Epon 812, sectioned at 0.5 micron, stained with toluidine blue, and evaluated by stereology for number and size of Leydig cells. Specimens from control and high dose groups were prepared for electron microscopy to quantify Leydig cell organelle content. TCDD treatment reduced (P < 0.01) body weight in a dose-dependent fashion. Testicular weight was not significantly reduced by TCDD treatment. The volume of Leydig cell cytoplasm per testis was reduced (P < 0.01) four weeks after treatment. Reduction in total Leydig cell volume resulted from a reduced (P < 0.05) number of Leydig cells and a reduced (P < 0.01) size of individual Leydig cells. However, the volume density (percentage) of Leydig cells occupied by specific organelles was not influenced by TCDD treatment. As a result of reduced total Leydig cell volume with no change in volume density of organelles in Leydig cells, the volumes per testis of smooth endoplasmic reticulum and mitochondria were reduced (P < 0.01) by TCDD treatment. In conclusion, the TCDD-induced reduction in Leydig cell volume per testis is explained by reduced number and size of individual Leydig cells and resulted in a significant reduction in total volume of both Leydig cell smooth endoplasmic reticulum and mitochondria per testis. Reduction in content of organelles that are responsible for various key steps in steroidogenesis, could explain TCDD-reduced production of testosterone in rats.