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Published on: October 11, 2015
Approaches to oocyte meiotic arrest in vitro and impact on oocyte developmental competence
Dulama Richani1, Robert B Gilchrist1
1Fertility & Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW, Australia.
Abstract:
Oocytes are maintained in a state of meiotic arrest following the first meiotic division until ovulation is triggered. Within the antral follicle, meiotic arrest is actively suppressed in a process facilitated by the cyclic nucleotides cGMP and cAMP. If removed from this inhibitory follicular environment and cultured in vitro, mammalian oocytes undergo spontaneous meiotic resumption in the absence of the usual stimulatory follicular stimuli, leading to asynchronicity with oocyte cytoplasmic maturation and lower developmental competence. For more than 50 years, pharmacological agents have been used to attenuate oocyte germinal vesicle (GV) breakdown in vitro. Agents that increase intra-oocyte cAMP or prevent its degradation have been predominantly used; however, agents such as kinase and protein synthesis inhibitors have also been trialed. Twenty years of research demonstrates that maintaining GV arrest for a period before in vitro maturation (IVM) improves oocyte developmental competence, and is likely attributed to maintenance of bidirectional communication with cumulus cells leading to improved oocyte metabolic function. However, outcomes are influenced by various factors including the mode of action of the modulators, dose, treatment duration, species, and the degree of hormonal priming of the oocyte donor. Cyclic GMP and/or cAMP modulation in a prematuration step (called pre-IVM) prior to IVM has shown the greatest consistency in improving oocyte developmental competence, whereas kinase and protein synthesis inhibitors have proven less effective at improving IVM outcomes. Such pre-IVM approaches have shown potential to alter current use of artificial reproductive technologies in medical and veterinary practice.
Insights
Maintaining oocyte meiotic arrest using cyclic GMP and/or cyclic AMP modulation before in vitro maturation (IVM) significantly improves developmental competence. This pre-IVM approach enhances oocyte quality for assisted reproductive technologies.
Area of Science:
- Reproductive Biology
- Cellular Signaling
- Developmental Biology
Background:
- Oocytes remain arrested in meiosis I until ovulation, with cyclic nucleotides (cGMP, cAMP) regulating this arrest within the follicle.
- In vitro culture without follicular support causes spontaneous meiotic resumption, leading to asynchronous maturation and reduced developmental potential.
- Pharmacological agents have been used for decades to inhibit germinal vesicle breakdown (GVBD) in vitro, primarily targeting cAMP levels.
Purpose of the Study:
- To evaluate the efficacy of modulating cyclic nucleotides (cGMP and/or cAMP) during a pre-in vitro maturation (pre-IVM) step to enhance oocyte developmental competence.
- To compare the effectiveness of cyclic nucleotide modulation with other agents like kinase and protein synthesis inhibitors for improving in vitro maturation (IVM) outcomes.
- To explore the potential of pre-IVM strategies to improve assisted reproductive technologies in human and veterinary medicine.
Main Methods:
- Investigated the use of pharmacological agents to modulate intra-oocyte cyclic GMP (cGMP) and cyclic adenosine monophosphate (cAMP) levels.
- Administered these modulators during a prematuration phase (pre-IVM) before standard in vitro maturation (IVM).
- Assessed the impact of pre-IVM treatments on oocyte developmental competence, comparing outcomes with kinase and protein synthesis inhibitors.
Main Results:
- Modulation of cGMP and/or cAMP during pre-IVM consistently improved oocyte developmental competence compared to standard IVM.
- Kinase and protein synthesis inhibitors were less effective in enhancing IVM outcomes.
- The effectiveness of pre-IVM is influenced by modulator type, dosage, duration, species, and hormonal priming.
Conclusions:
- Pre-IVM strategies involving cyclic nucleotide modulation offer a promising approach to enhance oocyte quality and developmental potential.
- This method supports bidirectional communication with cumulus cells, improving oocyte metabolic function and GV arrest maintenance.
- Optimized pre-IVM protocols hold significant potential for advancing current assisted reproductive technologies.
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