PARENT SESSION
SLIDE SESSION 6: REPRODUCTIVE TOXICOLOGY IN THE MALE AND FEMALE
Chairs: Janice Bailey, Rao Veeramachaneni, Christina Borgeest (Trainee)
Univ Ottawa-Monpetit 203
2:30 PM-4:30 PM

INHALATION EXPOSURE TO TRICHLOROETHYLENE CAUSES ALTERED PATTERNS OF SPERMATOGENESIS AND REDUCED LEYDIG CELL FUNCTION.

Wade, Michael¹, McMahon, Avril¹, Lee, Alice¹, Bjarnason, Stephen¹, Vincent, Renaud¹, ¹

ABSTRACT- Trichloroethylene (TCE) is a solvent which is widely used for degreasing metal and human exposure by the inhalation route is very extensive. While the data from experimental or epidemiological studies are limited, there are some indications that inhalation exposure to this substance causes toxicity to the male reproductive tract. Studies were initiated to determine the effects of subacute whole body exposure to TCE on the dynamics of spermatogenesis and ex vivo Leydig cell function in sexually mature mice (CD-1, 32-45 g). Mice were exposed to atmospheres containing 1500 ppm for 6 hr per day for 3 days (approximately 3450 mg/kg/day assuming 100% absorption) or 1000 ppm TCE for 6 hr per day 5 days per week (equivalent to approximately 2300 mg/kg/day) for 2 to 4 weeks. Treatment for 3 days had no effect on body or organ weights, except for a significant increase in liver weight, or on the condensation of nuclei as assessed by differential acridine orange staining of acid treated epididymal sperm. The spermatogenic cells were dispersed and populations resolved and quantified using a flow cytometric method based on binding of fluorochromes indicating DNA content (propidium iodide) and mitochondria (nonyl acridine orange). TCE exposure for 3 days led to a 45% decrease (p<0.05) in the proportion of primary spermatocytes (excluding pachytene spermatocytes) and trend towards a decrease in pachytene spermatocytes (23%, p=0.08). After 2 weeks of exposure, there was a significant increase in both populations of primary spermatocytes while round spermatids were reduced. All of these changes resolved within a week post exposure while a reduction in secondary spermatocytes persisted for 2 weeks post exposure. An enriched Leydig cell preparation, isolated from TCE exposed animals produced less testosterone, than comparable cells from control animals in response all doses of human chorionic gonadotropin tested. The TCE-induced lesion in steroidogenesis was also seen in 4 week exposed animals and was evident beyond the level of receptor activation as testosterone production in response to cAMP-agonist dibutyryl cAMP was also reduced in TCE-treated animals relative to controls. These studies suggest that TCE treatment suppresses Leydig cell function and causes subtle changes in dynamics of spermatogenesis.

KEY WORDS: Trichloroethylene, Spermatogenesis, Leydig cell, Testicular toxicity