Attenuation of 2-methoxyethanol-induced testicular toxicity in the rat by simple physiological compounds.
2-Methoxyethanol (2-ME) is an industrial solvent which is toxic to both male and female reproductive systems of laboratory animals. Earlier data have demonstrated that the developmental toxicity of 2-ME can be attenuated by simple physiological compounds such as serine, acetate, sarcosine, glycine, and D-glucose. The present experiments were designed to evaluate the same compounds for their ability to ameliorate the testicular toxicity that occurs in rats after 2-ME exposure. The extent of testicular damage was assessed by quantitating daily sperm production (DSP) on Day 24 following a single dose of 2-ME (6.6 mmol/kg, 500 mg/kg). Serine completely eliminated 2-ME-induced decreases in DSP, while glucose was without effect. Acetate, sarcosine, and glycine were of similar efficacy resulting in DSP that was significantly greater than that observed in rats which received 2-ME alone. Histopathological studies revealed that 2-ME treatment resulted in stage-specific degeneration of late stage pachytene spermatocytes 24 hr after treatment. No apparent degenerative changes occurred after concurrent treatment with serine. Similarly, serine also prevented the decreased number of spermatids in the lumina of the seminiferous tubules on Day 24 after 2-ME exposure alone. All of the compounds utilized in this study are linked to oxidation pathways involving tetrahydrofolic acid as a catalyst for one-carbon moiety transfer into purine and pyrimidine bases which are necessary precursors for DNA and RNA synthesis. The ability of these compounds to attenuate the testicular toxicity of 2-ME may result from their ability to donate one-carbon units which can be used in purine base biosynthesis. Reduced availability of bases would be expected to affect late stage pachytene spermatocytes which are known to be undergoing rapid RNA synthesis.
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Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Welsch
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D000818:Animals; D004347:Drug Interactions; D005026:Ethylene Glycols / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012521:Sarcosine / Q000494:pharmacology; D012694:Serine / Q000494:pharmacology; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology
D005026:Ethylene Glycols; D012694:Serine; C005219:methyl cellosolve; D005947:Glucose; D005998:Glycine; D012521:Sarcosine