Resveratrol reestablishes spermatogenesis after testicular injury in rats caused by 2, 5-hexanedione.
BACKGROUND
Environmental toxins can destroy the physiological process of spermatogenesis and even lead to male infertility. Resveratrol (RES) is a natural phytoalexin with a wide range of biological activities. Some recent researches have demonstrated that RES can increase sperm output and protect sperm from apoptosis caused by physical damage. However, there is no evidence indicating that it can also exhibit a similar activity in testis injury caused by environmental toxins. This study was designed to evaluate the protective effect of resveratrol on testis damaged by environmental toxins and to elucidate the possible mechanism of its protective effect.


METHODS
In this study 2, 5-hexanedione (2, 5-HD) was used as the injury agent. Forty male SD rats were randomly divided into 5 groups. During the first 5 weeks, group A was raised normally, groups B, C, D and E were exposed to 1% 2, 5-HD; during the following 9 weeks, group C, D, E received intragastric administration of different concentrations of resveratrol (20 mg x kg(-1) x d(-1), 40 mg x kg(-1) x d(-1) and 80 mg x kg(-1) x d(-1)), while groups A and B were treated by carboxymethylcellulose. Physical signs, body weight gain and testis weight were comparatively observed. Numbers and diameters of seminiferous tubules were analyzed following HE staining. In addition, expression of the c-kit protein and gene in spermatogenic cells in every group was detected with immunohistochemistry, Western blot or RT-PCR.


RESULTS
The 2, 5-HD treatment resulted in physical signs that became worse and in emarciated testis. HE staining and immunohistochemistry showed that seminiferous tubules became emarcid, obsolete spermatogonia being stagnant and expression of c-kit protein being depressed. After oral administration of resveratrol, the 2, 5-HD-induced physical signs were improved and close to the normal rats. The gain of body weight increased (P < 0.01). The recovery of testis weight was significant (P < 0.01). At the histological level, the seminiferous epithelia began to differentiate (P < 0.01); and even the physiological process of spermatogenesis restarted. Moreover, expression of c-kit protein and gene function resumed, although its expression remained different from the normal group. The diameter of and number of seminiferous tubules and the expression level of c-kit protein and gene activity were much closer to the normal group with increased doses of the resveratrol through oral administration.


CONCLUSIONS
Resveratrol could ameliorate markedly the dyszoospermia induced by 2, 5-HD and induce spermatogenesis. The expression of c-kit, which is a specific marker protein of spermatogenic cell membranes, could be regulated by resveratrol.
Jiang
Yong-guang
YG
Department of Urology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. yongguangjiang@yahoo.com.cn
Peng
Tao
T
Luo
Yong
Y
Li
Ming-chuan
MC
Lin
Yun-hua
YH
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006588:Hexanones / Q000633:toxicity*; D007150:Immunohistochemistry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012671:Seminiferous Tubules / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D013737:Testis / Q000187:drug effects*
D006588:Hexanones; D012333:RNA, Messenger; D013267:Stilbenes; C011269:2,5-hexanedione; D019009:Proto-Oncogene Proteins c-kit; D000077185:Resveratrol