The effect of 2-methoxyethanol and methoxyacetic acid on sertoli cell lactate production and protein synthesis in vitro

Abstract

Exposure to 2-methoxyethanol (ME) or its major metabolite, methoxyacetic acid (MA), results in spermatocyte depletion and testicular atrophy in experimental animals. The site of spermatogenesis is within the seminiferous tubule. Sertoli cells support spermatogenesis, synthesizing and secreting proteins, and metabolic substrates for utilization by differentiating germ cells in the seminiferous tubule lumen. One of these substrates, lactate, is preferentially metabolized by spermatocytes. Therefore, because germ cells are dependent upon the metabolic products of Sertoli cells, the effect of ME and MA on production of lactate and protein synthesis was measured in cultured rat Sertoli cells. Cell cultures were incubated with ME or MA at 0, 3, or 10 mM for up to 12 hr. No significant difference was seen in total protein synthesis as measured by [3H]leucine incorporation. ME and MA had no apparent effect on cell viability. However, lactate concentrations and rates of lactate accumulation were significantly decreased by MA, but not ME, at both 3 and 10 mM following incubation for 6, 9, and 12 hr. The results suggest that inhibition of Sertoli cell lactate production resulting from ME or MA exposure could account for the inhibitory action of these compounds on spermatogenesis.

Rat Pachytene Spermatocytes Down-Regulate a Polo-Like Kinase and Up-Regulate a Thiol-Specific Antioxidant Protein, Whereas Sertoli Cells Down-Regulate a Phosphodiesterase and Up-Regulate an Oxidative Stress Protein after Exposure to Methoxyethanol and Methoxyacetic Acid

“…The Sertoli cell metabolizes glucose, primarily to lactate (15), a primary metabolic substrate of cells early in the spermatogenic cycle (16,17). ME and MAA induce changes in Sertoli cell lactate concentration and in cyclic protein-2, raising the possibility that the degradation of pachytene sper-matocytes results from alterations in Sertoli cell function (18,19).…”

Integrated NMR-Based Metabonomic Investigation of Early Metabolic Effects of Ethylene Glycol Monomethyl Ether (Egme) on Male Reproductive Organs in Rats

“…On another route, lactate is also uptaken by pachytene spermatocytes from blood using MCT1. EGME is a specific toxicant to spermatocytes, but methoxyacetic acid (MAA), which is the major metabolite of EGME, also inhibits lactate production in Sertoli cells in vitro (Beattie et al, 1984). Under normal conditions, the intracellular concentration of lactate is regulated by hormonal control and supply.…”

Health hazard evaluation report: HETA-84-474-1946, Electric Boat Division, General Dynamics Corporation, Groton, Connecticut.

“…Extensive animal studies indicate that the aldehyde and/or acid metabolites of glycol ethers produce testicular toxicity and infertility in males (Beattie et al, 1984;Chapin and Lamb, 1984;Cn:~sy and Foster, 1984;Creasy et al, 1985;Foster et al, 1984Foster et al, , 1986Foster et al, , 1987Hurtt and Zenick, 1986;Oudiz and Zenick, 1986) and embryoto~icity and developmen~ anomalies in pregnant females (Anderson et al, 1987;Andersen andHardin et al, 1984, 1987;Hawley et al, 1984a,b;Hardin and Eisenman, 1987;Johnson et al, 1984;Tyler et al, 1984;Wier et al, 1987;Zenick et al, 1984). This report lays the groundwork for a quantitative assessment of these effects in human workers.…”