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EFFECTS OF HEAT AND BROMOCHLOROACETIC ACID ON MALE REPRODUCTION IN HEAT SHOCK FACTOR-1 GENE KNOCKOUT MICE
Citation:
Luft, J. C., I. J. Benjamin, J B. Garges, AND D J. Dix. EFFECTS OF HEAT AND BROMOCHLOROACETIC ACID ON MALE REPRODUCTION IN HEAT SHOCK FACTOR-1 GENE KNOCKOUT MICE. Presented at Society of Toxicology, San Francisco, CA, March 25 - 29, 2001.
Description:
Effects of heat and bromochloroacetic acid on male reproduction in heat shock factor-1 gene knockout mice.
Luft JC1, IJ Benjamin2, JB Garges1 and DJ Dix1. 1Reproductive Toxicology Division, USEPA, RTP, NC, 27711 and 2Dept of Internal Medicine, Univ.of Texas Southwestern Med Center, Dallas, TX, 75235
Sponsor: G Klinefelter
Haloacetic acids (HA) are unintended by-products of drinking water disinfection and bromochloroacetic acid (BCA), a commonly occurring HA, has been identified as a male reproductive toxicant in adult male mice. Heat shock proteins (HSPs) are critical components of a highly conserved cellular defense mechanism that protects cells from environmental exposures including hyperthermia, oxygen free radicals, heavy metals, and infection. During the stress response in mouse testis, expression of inducible HSPs is regulated by activation of heat shock transcription factor1 (HSF1). In this study we examined the effects of HSF1 gene knockout on spermatogenesis following exposure to heat or BCA. Adult hsf-1+/+ (WT) and hsf-1-/- (KO) 129 SvEv/BALBc males were exposed to 251C or 431C, or exposed to 0-216 mg/kg BCA for 14 days. After dosing, males were used in a 40-day sequential breeding assay to determine if heat and/or BCA negatively affected reproductive performance by targeting a particular phase of spermatogenesis. Results indicated that neither WT nor KO males were susceptible to BCA exposure. However, 431C exposure reduced litters/male and number of fetuses/male in both WT and KO males from 20- 33 days after heat shock, indicating heat targets spermatocytes. Mating results from days 34-40 after heat shock indicated WT were recovering, while KO were not. To further examine this recovery, mice were put through an additional 10-day mating study starting 12 weeks after heat shock. KO males continued to have reduced litters/male and fetuses/male, suggesting an inability to recover from heat shock. These data indicate the ability to mount a heat shock response is essential for recovery of testicular cells from toxicant exposure. (This is an abstract of a proposed presentation and does not necessarily reflect EPA policy)