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Updated: Apr 12, 2026
Manipulation and In Vitro Maturation of Xenopus laevis Oocytes, Followed by Intracytoplasmic Sperm Injection, to Study Embryonic Development
Published on: February 9, 2015
Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes
Satoshi Sugimura1, Lesley J Ritter2, Ryan D Rose2
1Robinson Research Institute, and Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, The University of Adelaide, South Australia 5005, Australia; Institute of Agriculture, Department of Biological Production, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Abstract:
Oocytes acquire developmental competence with progressive folliculogenesis. Cumulus oocyte complexes (COCs) from small antral follicles have inherent low competence and are poorly responsive to amphiregulin (AREG) which normally mediates oocyte maturation and ovulation. Using low competence porcine COCs, in an in vitro AREG-induced oocyte maturation system, the combined exposure to N(6),2'-O-dibutyryladenosine 3':5' cyclic monophosphate (cAMP) and bone morphogenetic protein 15 (B15) and growth differentiation factor 9 (G9) was necessary to enhance the rate of oocyte meiotic maturation and blastocyst formation. Furthermore, the combination of cAMP+B15+G9 enabled AREG-stimulated cumulus expansion and increased expression of the matrix-related genes HAS2, TNFIPA6 and PTGS2. Additionally, the combination enhanced p-ERK1/2 which is downstream of the EGF receptor. The enhanced nuclear maturation and blastocyst formation rates with the combinational treatment were ablated by an EGF receptor phosphorylation inhibitor. These results indicate that cAMP and oocyte-secreted factors cooperate to promote EGF receptor functionality in developing COCs, representing a key component of the acquisition of oocyte developmental competence.
Insights
Low developmental competence in oocytes can be overcome. Combining cyclic adenosine monophosphate (cAMP) with bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) enhances oocyte maturation and embryo development.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Cellular Signaling
Background:
- Oocyte developmental competence is crucial for successful reproduction and is acquired during folliculogenesis.
- Cumulus oocyte complexes (COCs) from small follicles exhibit low competence and poor response to amphiregulin (AREG), a key mediator of maturation and ovulation.
Purpose of the Study:
- To investigate methods for enhancing the developmental competence of low-competence porcine COCs.
- To elucidate the roles of cyclic adenosine monophosphate (cAMP), bone morphogenetic protein 15 (BMP15), and growth differentiation factor 9 (GDF9) in AREG-induced oocyte maturation.
Main Methods:
- Utilized an in vitro system with low-competence porcine COCs.
- Applied combined exposure to cAMP, BMP15, and GDF9 during AREG-induced maturation.
- Assessed oocyte meiotic maturation, blastocyst formation, cumulus expansion, gene expression (HAS2, TNFIPA6, PTGS2), and extracellular signal-regulated kinase (ERK) phosphorylation.
Main Results:
- Combined cAMP, BMP15, and GDF9 significantly enhanced oocyte meiotic maturation and blastocyst formation rates.
- This combination also promoted AREG-stimulated cumulus expansion and upregulated key matrix-related genes.
- Enhanced phosphorylation of ERK1/2 (p-ERK1/2), downstream of the EGF receptor, was observed, and its inhibition abolished the beneficial effects.
Conclusions:
- cAMP and oocyte-secreted factors (BMP15, GDF9) synergistically promote EGF receptor signaling in COCs.
- This cooperative signaling is essential for enhancing EGF receptor functionality and acquiring developmental competence in oocytes.
- The findings highlight a critical mechanism for improving oocyte quality and developmental potential.
