Specificity of Epidermal Growth Factor Action on Maturation of the Murine Oocyte and Cumulus Oophorus in Vitro1

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Abstract
Experiments were carried out to determine the specificity of growth factor action on maturation of the oocyte-cumulus cell complex in vitro. Cumulus cell-enclosed oocytes (CEO) from primed mice were maintained in meiotic arrest in vitro with hypoxanthine (HX) and treated with one of ten different growth-promoting factors. The percentage of germinal vesicle breakdown (GVB) in the HX controls ranged from 44 to 64.7% after 21-22 h. Oocytes responded to treatment with growth-promoting factors in one of three ways: (1) no response; (2) low response; or (3) high response. The nonresponding groups included transforming growth factor-.beta., platelet-derived growth factor, bombesin, sodium orthovanadate, nerve growth factor, and insulin-like growth factors I and II, each of which had no statistically significant effect on GVB. Insulin and fibroblast growth factor were members of the low response group and stimulated increases in GVB of 21.2 24.9%. Epidermal growth factor (EGF) was the only factor that produced a high frequency of maturation in the CEO; 100% of the arrested CEO were stimulated to undergo GVB in response to EGF treatment (a 51% increase over controls). No interaction was observed when EGF was tested with follicle-stimulating hormone (FSH) on hormone-induced GVB. When tested for an action on cumulus cell expansion, EGF was the only growth-promoting factor that triggered this response and did so more effectively than FSH. Heparin suppressed cumulus expansion in both EGF- and FSH-treated CEO, but did not prevent GVB stimulated by either hormone. These results lead to the conclusions that (1) a specificity exists for EGF-like molecules in the maturation of the oocyte as well as the cumulus oophorus, and that (2) cumulus expansion and oocyte maturation do not appear to be casually related in hormonally stimulated CEO in vitro.