Effect of cocaine on germ cell apoptosis in rats at different ages.
OBJECTIVE
To investigate the effect of cocaine on apoptosis and caspase-3 activity in germ cells in male rats at different ages.


METHODS
Cocaine hydrochloride was given (15 mg/kg body weight s.c.) to male Sprague-Dawley rats of 3 weeks (n = 8), 6 weeks (n = 8) and 12 weeks (n = 8) of age, daily for 28 Days. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estrogen (E2) were assayed, and the DNA fragmentation of germ cells was determined by gel eletronphoresis. The cell cycle, apoptosis and caspase-3 activity of germ cells were tested by flow cytometry.


RESULTS
After the 28-day cocaine treatment, testes weight of the 3-week-old rats, the testes and body weights of the 6-week-old rats were decreased significantly compared to those of their corresponding controls (P < 0.05). The serum level of T was decreased significantly in the 3-week-old and 6-week-old rats, and the serum level of PRL was also decreased significantly in 12-week-old rats compared to the controls (P < 0.05). In all the three cocaine-treated groups, the isolated DNA displayed a clear ladder pattern, especially in the 6-week old rats. The number of apoptosic germ cells increased significantly in 3- and 6-week-old rats treated with cocaine (P < 0.05). The caspase-3 activity in all three groups increased significantly compared to the controls (P < 0.05), especially in the 6-week-old rats.


CONCLUSIONS
Cocaine exposure for 28 Days leads to significant damage to male gonad and apoptosis elevation in testes of rats of different ages, especially in those of 6 weeks of age. The increase in caspase-3 activity might be a key pathway related to the early stage of apoptosis as the mechanism of cocaine-induced germ cell loss.
Yang
Guo-Sheng
GS
Department of Urology, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China. yang_guosheng@163.com
Wang
Wei
W
Wang
Yi-Min
YM
Chen
Zhao-Dian
ZD
Wang
Shuo
S
Fang
Jia-Jie
JJ
D000375:Aging / Q000502:physiology; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004967:Estrogens / Q000097:blood; D005640:Follicle Stimulating Hormone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013094:Spermatozoa / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood
D004967:Estrogens; D013739:Testosterone; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003042:Cocaine