PARENT SESSION
TOXICOLOGY

Monday, August 2, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(91) STUDY ON THE TOXIC MECHANISM OF 3-MCPD IN MALE FERTILITY.

Kwack, Seung Jun ¹, Kim, Soon Sun¹, Rhee, Gyu Seek¹, Lee, Rhee Da¹, Seok, Ji Hyun¹, Chae, Soo Yeong¹, Choi, Yo Woo ¹, Kim, Bo Ra ¹, Cho, Dae Hyun¹, Park, Kui Lea¹, ¹ National Institute of Toxicological Research, Seoul, Korea

ABSTRACT- 3-Monochloro-1,2-propanediol(3-MCPD) is a food contaminant, often found in different foods containing acid hydrolyzed(AH) protein, like seasonings and savory food products. In previous study, paternal administration with 3-MCPD resulted in adverse effects on male fertility. Sperm motility, copulation index and fertility index were markedly decreased and numbers of live fetuses showed steep dose-response curves. These results suggested that 3-MCPD induced spermatotoxic effect, which caused a antifertility on male rat. The purpose of the present study was to investigate the mechanisms of 3-MCPD on spermatotoxicity. In vitro hormone assay was performed for observing the adverse effect of 3-MCPD on the production of hormone(luteinizng hormone and testosterone). 0.1-50 mg/kg bw of 3-MCPD were given daily by gavage to groups of 5 immature male rats(PND21) for 2 weeks. At the end of pre-treatment period, hormone levels were measured in serum and testes. Also, In vitro hormone assay was performed in Leydig cell culture system. To evaluate the effects on induction of apoptosis in testes and alteration of H⁺-ATPase level in cauda epididymides, 10 or 100 mg/kg bw of 3-MCPD were treated by gavage to adult male rat and then testes and epididymides were taken at 3, 6, 12 and 24 h after the rat received a 3-MCPD. In results, significant changes of related hormones were not observed by treatment of 3-MCPD. Apoptosis was not detected in the testes treated acute high dose of 3-MCPD by DNA fragmentation assay, TUNEL assay and caspase-7 activity test. But, H⁺-ATPase level in cauda epididymis was decreased by treatment of 3-MCPD. These results indicate that spermatotoxic effect induced by 3-MCPD is mediated by diminution of H⁺-ATPase expression in cauda epididymidis, and suggest that alteration of pH level in cauda epididymides by H⁺-ATPase lead to disturb a sperm maturation including acquisition of motility.

KEY WORDS: sperm motility, spermatotoxicity, ATPase, 3-MCPD