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- W2078397599 abstract "Granulosa cells supply the germinal vesicle (GV) oocyte with sufficient cGMP to maintain meiotic arrest until gap junctions close allowing cGMP-inhibited PDE 3A to become active and decrease intra-oocyte cAMP. Previously we have demonstrated that PDE9 is the cGMP degrading enzyme in the oocyte and that exogenous cGMP coupled with a PDE9 inhibitor will delay the timing of meiotic resumption. The objective for this study was to determine if oocytes able to mature in vitro under these culture conditions are capable of undergoing normal fertilization. Controlled non-human primate experiment. Mature female rhesus macaques underwent controlled ovarian stimulation. Laparoscopic follicle aspiration was performed prior to an ovulatory stimulus to recover germinal vesicle (GV) intact oocytes. GV oocytes were separated free of mural and cumulus granulosa cells and incubated for 24 hours in HECM-9 media in the absence (control) or presence (treated) of 10 mM 8-Br-cGMP (a membrane-permeable analogue of cGMP) to inhibit meiosis and elevate intra-oocyte cGMP. After 24 hours, treated oocytes were washed and placed into fresh HECM-9 containing 0 (T-0) or 1 mM BAY 73-6691 (PDE9 inhibitor, T-I) for an additional 24 hours. Control and treated MII ova underwent standard in vitro fertilization. The criterion for normal fertilization was pronuclear formation after 17 hours. There was no difference in the proportion of control 12/20 (60%) and T-0 4/8 (50%, P=1.0) oocytes that progressed to MII at 24 and 48 h respectively. In contrast none of the T-I oocytes incubated in the presence of the 1 mM PDE-9 inhibitor progressed to MII 0/9 (0%, P<0.05). Of the control MII ova, 7/12 (58%) fertilized compared with none of the cGMP-treated oocytes. Increasing the concentration of cGMP in the oocyte is associated with a delay in oocyte maturation and this negatively affects fertilization. Strategies that increase cGMP in the oocyte may have contraceptive potential." @default.
- W2078397599 created "2016-06-24" @default.
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- W2078397599 date "2011-09-01" @default.
- W2078397599 modified "2023-09-30" @default.
- W2078397599 title "Incubation of cGMP-primed macaque oocytes with a phosphodiesterase 9 inhibitor prevents nuclear maturation and in vitro fertilization" @default.
- W2078397599 doi "https://doi.org/10.1016/j.fertnstert.2011.07.146" @default.
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