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Inhibition of germinal vesicle breakdown in Xenopus oocytes in vitro by a series of substituted glycol ethers
Author(s) -
Fort Douglas J.,
Mathis Michael B.,
Guiney Patrick D.,
Weeks John A.
Publication year - 2018
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3567
Subject(s) - germinal vesicle , ethylene glycol , ether , chemistry , triethylene glycol , biochemistry , organic chemistry , meiosis , gene
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.