Assessment of the reproductive toxicity of inhalation exposure to ethyl tertiary butyl ether in male mice with normal, low active and inactive ALDH2.
No data are available regarding aldehyde dehydrogenase 2 (ALDH2) polymorphisms related to the reproductive toxicity possibly caused by ethyl tertiary butyl ether (ETBE). In this study, two inhalation experiments were performed in Aldh2 knockout (KO), heterogeneous (HT) and wild type (WT) C57BL/6 male mice exposed to ETBE, and the data about general toxicity, testicular histopathology, sperm head numbers, sperm motility and sperm DNA damage were collected. The results showed that the 13-week exposure to 0, 500, 1,750 and 5,000 ppm ETBE significantly decreased sperm motility and increased levels of sperm DNA strand breaks and 8-hydroxy-deoxyguanosine in both WT and KO mice, the effects were found in 1,750 and 5,000 ppm groups of WT mice, and all of the three exposed groups of KO mice compared to the corresponding control; furthermore, ETBE also caused decrease in the relative weights of testes and epididymides, the slight atrophy of seminiferous tubules of testis and reduction in sperm numbers of KO mice exposed to ≥500 ppm. In the experiment of exposure to lower concentrations of ETBE (0, 50, 200 and 500 ppm) for 9 weeks, the remarkable effects of ETBE on sperm head numbers, sperm motility and sperm DNA damage were further observed in KO and HT mice exposed to 200 ppm ETBE, but not in WT mice. Our findings suggested that only exposure to high concentrations of ETBE might result in reproductive toxicity in mice with normal active ALDH2, while low active and inactive ALDH2 enzyme significantly enhanced the ETBE-induced reproductive toxicity in mice, even exposed to low concentrations of ETBE, mainly due to the accumulation of acetaldehyde as a primary metabolite of ETBE.
Japan National Institute of Occupational Safety and Health, Kawasaki, Japan.
Zuquan
Z
Weng
Katsumi
K
Ohtani
Megumi
M
Suda
Yukie
Y
Yanagiba
Toshihiro
T
Kawamoto
Tamie
T
Nakajima
Rui-Sheng
RS
Wang
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000444:Aldehyde Dehydrogenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001711:Biotransformation; D020552:Comet Assay; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005019:Ethyl Ethers / Q000378:metabolism / Q000633:toxicity*; D005298:Fertility / Q000187:drug effects*; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D018570:Risk Assessment; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D015415:Biomarkers; D005019:Ethyl Ethers; C098546:ethyl tert-butyl ether; D000080242:8-Hydroxy-2'-Deoxyguanosine; C515029:ALDH2 protein, mouse; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D003849:Deoxyguanosine