Impairment of spermatogenesis in rats by methylmercury: involvement of stage- and cell- specific germ cell apoptosis.
Methylmercury has been shown to affect the male reproductive organs. However, the specific mode of impairment of spermatogenesis during methylmercury exposure remains unknown. In this study, we characterized the induction of germ cell apoptosis and reproductive toxicity in Wistar male rats that had been exposed to methylmercuric chloride (MMC). Subcutaneous injection of MMC at a dose of 10 mg/kg per day for 8 days resulted in a 28% testicular weight loss at 14 days after the first injection. In addition, the ventral and dorso-lateral prostatic lobes showed a 65 and 52% decrease, respectively, at 14 days, although no effects were observed in the epididymis. Sperm production also was suppressed by the administration of MMC. After exposure to MMC, fragmentation of testicular DNA was found to be increased at 3 days after the first injection, with a 20-fold increase over control levels at 14 days. In situ detection of apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) staining revealed that spermatocytes and spermatids at stages VII-VIII and IX-XI, respectively, steps which are considered to be highly sensitive to testosterone, were the major cell types affected. Consequently, a marked cell loss in elongated spermatids at stages XII-XIV and I was observed at 14 days. In addition, plasma testosterone levels were reduced at 6 days after exposure to MMC, and remained at approximately 20% of control levels during the 14-day observation period. Our results suggest that methylmercury impairs spermatogenesis by germ cell deletion via cell- and stage- specific apoptosis.
Homma-Takeda
S
S
Graduate School Doctoral Program in Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. shino_ht@nirs.go.jp
Kugenuma
Y
Y
Iwamuro
T
T
Kumagai
Y
Y
Shimojo
N
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008297:Male; D008628:Mercury / Q000032:analysis; D008767:Methylmercury Compounds / Q000633:toxicity*; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013076:Sperm Count; D013091:Spermatogenesis / Q000187:drug effects* / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood
D008767:Methylmercury Compounds; D013739:Testosterone; D008628:Mercury; C004925:methylmercuric chloride