Beattie P J, Welsh M J, Brabec M J
Toxicol Appl Pharmacol. 1984 Oct;76(1):56-61. doi: 10.1016/0041-008x(84)90028-0.
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.
接触2-甲氧基乙醇（ME）或其主要代谢产物甲氧基乙酸（MA）会导致实验动物的精母细胞耗竭和睾丸萎缩。精子发生的部位在生精小管内。支持细胞支持精子发生，合成并分泌蛋白质以及代谢底物，供生精小管管腔内分化中的生殖细胞利用。其中一种底物乳酸，优先被精母细胞代谢。因此，由于生殖细胞依赖于支持细胞的代谢产物，于是在培养的大鼠支持细胞中测量了ME和MA对乳酸产生和蛋白质合成的影响。细胞培养物与0、3或10 mM的ME或MA孵育长达12小时。通过[3H]亮氨酸掺入法测定的总蛋白质合成未见显著差异。ME和MA对细胞活力无明显影响。然而，在孵育6、9和12小时后，3 mM和10 mM的MA均显著降低了乳酸浓度和乳酸积累速率，但ME没有此作用。结果表明，ME或MA暴露导致支持细胞乳酸产生受到抑制，这可能解释了这些化合物对精子发生的抑制作用。
