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J Appl Toxicol January 1, 2018; 38 (5): 628-637.

Inhibition of germinal vesicle breakdown in Xenopus oocytes in vitro by a series of substituted glycol ethers.

Fort DJ , Mathis MB , Guiney PD , Weeks JA .

A 24 hour in vitro Xenopus oocyte maturation (germinal vesicle breakdown [GVBD]) assay developed by Pickford and Morris (Environmental Health Perspectives, 1999, 107, 285-292) was used to screen a series of substituted glycol ethers (GEs). Substituted GEs included: ethylene glycol monomethyl ether (EGME); EG monoethyl ether (EGEE); EG monopropyl ether (EGPE); EG monobutyl ether (EGBE); EG monohexyl ether (EGHE); diethylene glycol monomethyl ether (DGME); triethylene glycol monomethyl ether (TGME); ethylene glycol monophenyl ether (EGPhE); EG monobenzyl ether (EGBeE); EG diphenyl ether (EGDPhE); and propylene glycol monophenyl ether (PGPhE). The GEs inhibited progesterone- or androstenedione-induced GVBD with the following relative potency: EGPhE > PGPhE > EGME > EGEE ≥ EGBeE > EGPE > EGBE >EGHE > EGDPhE > DGME ≥ TGME, or EGPhE > PGPhE > EGBeE > EGDPhE > EGEE > EGME > EGPE > EGBE, EGHE, DGME and TGME, respectively. Further, [3 H]progesterone or [3 H]androstenedione binding affinities to the oocyte plasma membrane progesterone receptor (OMPR) or classical androgen receptor (AR) were: EGME > EGPhE ≥ PGPhE ≥ EGEE > EGBeE > EGPE > EGBE ≥ EGHE > EGDPhE, TGME, and DGME, or EGPhE > PGPhE > EGBeE > EGDPhE > EGEE ≥ EGME > EGPE, EGBE, and EGHE > DGME and TGME, respectively. Binary joint mixture studies with the GVBD model using flutamide (AR antagonist) and EGPhE indicated that flutamide/EGPhE mixture acted in a concentration additive manner. The effects of substituted GE series, however, may be mediated through the OMPR; the potency of EGPhE may be the result of bimodal inhibition of both the OMPR and AR pathways.

PubMed ID: 29205417
Article link: J Appl Toxicol

Genes referenced: ar mapk1 pgr rem1
GO keywords: oocyte maturation [+]

Article Images: [+] show captions

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