Reproductive Toxicity of Ethylene Glycol Monoethyl Ether in Aldh2 Knockout Mice

Abstract

Ethylene glycol monoethyl ether (EGEE) can cause damage to testes and sperm, and its metabolites are believed to play an important role in its toxicity. Aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of this chemical. To investigate whether and how the enzyme affects the toxicity of EGEE, we conducted experiments comparing Aldh2 knockout mice with wild-type mice. Administration of EGEE at 100 and 600 mg/kg/day for one week did not induce any significant change in the weight and body weight ratios of testes, prostate and epididymides in either Aldh2 knockout or wild-type mice. However, motion of sperm from the spermaduct, as analyzed with a Hamilton-Thorne Sperm analyzer, was slightly decreased in the low dose group, and significantly lower in the high dose group; and the percentage of progressive sperm was also reduced in the two EGEE groups. This effect of EGEE treatment was observed in the wild-type, but not in the Aldh2 knockout mice. Sperm motion from the cauda epididymides was not affected. On the other hand, the concentration of ethoxyacetic acid, a metabolite of EGEE, in 24 h pooled urine of EGEE-treated Aldh2 knockout mice was not significantly lower than that of the wild-type mice on most days of urine sampling. These results suggest that inactivation of the ALDH2 enzyme due to gene mutation may be linked to differences in the susceptibility to EGEE-induced sperm toxicity.

Induction of oxidative damage in the testes and spermatozoa and hematotoxicity in rats exposed to multiple doses of ethylene glycol monoethyl ether

“…The differences in these data may be due to differences in treatment duration, dose and mode of administration and/or to species differences. However, our result is consistent with Wang et al 7 who reported that administration of EGEE by oral gavage at 100 and 600 mg/kg/day for 1 week did not induce any significant change in the weight and body weights ratios of the testes, prostate and epididymis in mice.…”

“…6 Recently, it has been shown that susceptibility to EGEE-induced spermatozoa toxicity may differ according to the polymorphism of aldehyde dehydrogenase 2 (ALDH 2). 7 In addition, Starek et al 8 reported that no tolerance to EGEE-induced hemolysis developed upon repeated subcutaneous exposure of rats.…”

A Personalized Medicine Approach for Asian Americans with the Aldehyde Dehydrogenase 2*2 Variant

“…Glycol ether exposure may reduce sperm count in men (107). Knockout ALDH2 mice are more protected from ethylene glycol monoethyl ether–induced sperm toxicity compared to wild-type mice (108). Thus, the ALDH2*2 variant may protect against the effects of some types of organic solvents.…”

Nicotinamide Mononucleotide Restores the Meiotic Competency of Porcine Oocytes Exposed to Ethylene Glycol Butyl Ether

“…Recent studies have found that EGEE exposure causes the health risks including the damage to the liver, blood, and reproductive systems (Welsch, 2005;Scofield et al, 2006;Wang et al, 2006). Repeated exposure to EGEE causes testicular atrophy, reduced sperm count, and sperm motility retardation (Melnick, 1984;Wang et al, 2006Wang et al, , 2007. EGBE is rapidly absorbed through dermal, pulmonary, and gastrointestinal routes (Bauer et al, 1992).…”