Effect of Ethane 1,2-Dimethane Sulfonate(EDS) on the Testicular Expression of Steroidogenesis-related Genes and Epididymal Sperm Count in the Adult Rat

Jeon, Yoon; Kim, Soo Woong; Paick, Jae Seung; Lee, Sung Ho

Abstract

PURPOSE
Ethane 1,2-Dimethane sulfonate (EDS), an alkylating agent, has been widely used to create the testosterone withdrawal rat model. The present study was carried out to test the effect of EDS administration on the expression of steroidogenesis-related genes in the rat testis and on epididymal sperm counts.
MATERIALS AND METHODS
Adult male Sprague-Dawley rats (300~350 g B.W.) were injected with a single dose of EDS (75 mg/kg, i.p.) and sacrificed on days 0, 7, 14, 21, 28, 35, 42, and 49. Tissue weights (testis, epididymis and seminal vesicle) were measured, and serum LH levels were determined by specific radioimmunoassay. The transcriptional activities of LH receptor (LH-R), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), and steroidogenic acute regulatory protein (StAR) were evaluated by semi-quantitative RT-PCR.
RESULTS
Weights of the reproductive and accessory organs declined progressively after the EDS treatment (weeks 1~3). After this, the decrease stopped, with a gradual return towards normal. Full recovery was observed in testis and seminal vesicle evaluations on weeks 5 and 6, respectively. Only 70% recovery was found in epididymis during weeks 5~7. A more dramatic drop was observed in caput epididymal sperm count, and the maximum recovery was 40% on week 7. Serum LH level increased significantly on week 2 after EDS treatment, then gradually decreased during weeks 3~5. The transcripts for the steroidogenesis-related genes in testis declined sharply during weeks 1~2, then returned to normal on week 4.
CONCLUSIONS
Our results demonstrate that EDS might directly induce severe damage, such as tissue destruction and decreased sperm counts, in epididymis compared to those in testis and seminal vesicles. Changes in the activities of testicular steroidogenesis-related genes caused by abrupt death and repopulation of Leydig cells in EDS-treated rats were in good correlation with other parameters shown in this and previouslypublished data. Taken together, the EDS injection model might be useful to understand not only the mechanism of differentiation of testicular somatic and germ cells but also the function of the epididymis in the aging process.