Toxicity of Methoxyacetic Acid in Cultured Human Luteal Cells

Jennifer L. Almekinder , David E. Lennard , David K. Walmer , Barbara J. Davis
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Abstract

Ethylene glycol monomethyl ether (EGME) and its proximate metabolite, 2-methoxyacetic acid (MAA), increase ovarian luteal cell progesterone production in the female ratin vivoand in cultured rat luteal cellsin vitro,respectively. In order to better assess the potential hazard of EGME and MAA to women, these studies were conducted to determine whether the same concentrations of MAA increase progesterone in human luteinized granulosa cells as in rat luteal cells. Human cells were collected from healthy anonymous oocyte donors, washed, plated 25,000 viable cells per well, and treated with 10 IU hCG and 0–5 mmMAA for 6–48 hr. Progesterone in media was significantly elevated after 24 hr incubation at ≥1 mmMAA. MAA had no effect on ATP levels at 6 or 24 hr. Thus, MAA increased progesterone production in cultured human luteal cells at the same concentration as MAA increased progesterone in rat luteal cells. The implication is that EGME has the potential to alter ovarian luteal function in women. These data should be useful for determining the real health hazards and potential risks of EGME exposure.

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甲氧基乙酸对人黄体细胞的毒性研究
乙二醇单甲醚(EGME)及其近似代谢物2-甲氧基乙酸(MAA)分别在雌性大鼠体内和体外培养大鼠黄体细胞中增加卵巢黄体细胞孕酮的产生。为了更好地评估EGME和MAA对女性的潜在危害,进行了这些研究,以确定相同浓度的MAA是否会增加人黄体化颗粒细胞中的黄体酮,就像在大鼠黄体细胞中一样。从健康的匿名卵母细胞供体中收集人类细胞,清洗,每孔镀25,000个活细胞,并用10 IU hCG和0-5 mmMAA处理6-48小时。≥1 mmMAA孵育24小时后,培养液中黄体酮水平显著升高。MAA对6小时或24小时的ATP水平没有影响。因此,MAA增加培养的人黄体细胞中黄体酮的产生,其浓度与MAA增加大鼠黄体细胞中黄体酮的浓度相同。这意味着EGME有可能改变女性卵巢黄体功能。这些数据应有助于确定暴露于EGME的实际健康危害和潜在风险。
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