Cyclophosphamide treatment causes impairment of sperm and its fertilizing ability in mice.
This study is focused on the toxicological effect of cyclophosphamide on male mice reproductive system. In the present study, cyclophosphamide was injected intraperitoneally (ip) at the level of 50-200mg/kg body weight into 6-weeks old ICR male mice once in a week for a period of 5 weeks. The animals were sacrificed after 1st and 5th week of last injection. Reduction in weight of testis and epididymis were observed both in 1st and 5th week group mice after administration with increasing concentration of cyclophosphamide. The weight of the body significantly decreased in both 1st and 5th week group in mice treated with 200mg/kg cyclophosphamide. The weight of the testis significantly decreased with all doses of cyclophosphamide in 1st week group, whereas, in 5th week group significant reduction was observed only in 200mg/kg dose of cyclophosphamide. The sperm motility was analyzed with Computer-Assisted Sperm Analysis (CASA). The motility of caudal sperm decreased with increasing concentration of cyclophosphamide in the 1st week group, whereas, it revived after 5th week. The total sperm counts in the epididymis of 1st week group mice declined significantly while significant restoration of the same was observed with mice treated with 50,100 and 150 mg/kg doses in the 5th week group. The intact acrosome was lower with 150 and 200mg/kg doses in both 1st and 5th week group. The live sperm was reduced to 29% in mice treated with 200mg/kg in the 5th week group. The decrease in the pregnancy rate of female mice was 17, 50, 58 and 100% when mated with male mice injected with 50, 100, 150 and 200mg/kg dose, respectively. Seminiferous tubules of mouse testis were severely damaged in the 1st week group. However, reinstate of sperm within the seminiferous tubules was observed in the 5th week group mice. Significant decrease in serum luteinizing hormone (LH) was observed in the 1st week group treated with 50, 100, 150 and 200mg/kg dose of cyclophosphamide. However, no significant difference was observed in the serum follicle-stimulating hormone (FSH), whereas, a decrease of about 98% in serum testosterone level was observed in cyclophosphamide treated mice. The decrease in the mean testosterone levels of cyclophosphamide treated mice served as proof for the damage of testis. These results demonstrate that cyclophosphamide caused temporary interference of normal male reproductive system with low dose treatment, but might be permanent dysfunction in high dose treatment.
Elangovan
Namasivayam
N
Institute of Biochemical Science, College of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
Chiou
Tzeon-Jye
TJ
Tzeng
Woan-Fang
WF
Chu
Sin-Tak
ST
D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism; D020101:Acrosome Reaction / Q000187:drug effects; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000633:toxicity*; D005306:Fertilization / Q000187:drug effects*; D005640:Follicle Stimulating Hormone / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D013739:Testosterone / Q000097:blood
D018906:Antineoplastic Agents, Alkylating; D012333:RNA, Messenger; D013739:Testosterone; D003520:Cyclophosphamide; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme