Promotion of EGF receptor signaling improves the quality of low developmental competence oocytes

• Published in: Developmental biology Vol. 403; no. 2; pp. 139 - 149
• Main Authors: Sugimura, Satoshi, Ritter, Lesley J., Rose, Ryan D., Thompson, Jeremy G., Smitz, Johan, Mottershead, David G., Gilchrist, Robert B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-07-2015
• Subjects: Amphiregulin; Animals; BMP15; cAMP; Cyclic AMP - metabolism; Female; GDF9; Oocyte development; Oocytes - cytology; Oocytes - metabolism; Ovarian Follicle - metabolism; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction; Sus scrofa - physiology; GDF9; Oocyte development; Amphiregulin; cAMP; BMP15
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2015.05.008

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),2ʹ-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.
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•Oocytes from small follicles have low competence and are poorly responsive to AREG.•cAMP, B15 and G9 enable AREG-stimulated cumulus expansion.•The combination enhances signaling downstream of the EGF receptor.•Acquisition of EGFR responsiveness is associated with oocyte competence.•cAMP, B15 and G9 facilitate the acquisition of oocyte developmental competence.