Toxicity of methoxyacetic acid in cultured human luteal cells.
Ethylene glycol monomethyl ether (EGME) and its proximate metabolite, 2-methoxyacetic acid (MAA), increase ovarian luteal cell progesterone production in the female rat in vivo and in cultured rat luteal cells in 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 mM MAA for 6-48 hr. Progesterone in media was significantly elevated after 24 hr incubation at >/=1 mM MAA. 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.
Almekinder
J L
JL
Laboratory of Experimental Pathology, NIEHS, Research Triangle Park, North Carolina, 27709, USA.
Lennard
D E
DE
Walmer
D K
DK
Davis
B J
BJ
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005026:Ethylene Glycols / Q000633:toxicity; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis; D011863:Radioimmunoassay; D051381:Rats; D012997:Solvents / Q000633:toxicity
D000085:Acetates; D005026:Ethylene Glycols; D012997:Solvents; D011374:Progesterone; D000242:Cyclic AMP; C005219:methyl cellosolve; C013598:methoxyacetic acid