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 m 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 m 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.