Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade
The epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte ch...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1161813/full |
| _version_ | 1797852940909674496 |
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| author | J. G. Conte J. G. Conte M. L. Tellechea B. Park M. G. Ballerini G. Jaita G. Jaita M. C. Peluffo |
| author_facet | J. G. Conte J. G. Conte M. L. Tellechea B. Park M. G. Ballerini G. Jaita G. Jaita M. C. Peluffo |
| author_sort | J. G. Conte |
| collection | DOAJ |
| description | The epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte chemoattractant protein-1, MCP1) as novel mediators of the ovulatory cascade. Our previous results demonstrate that the gonadotropins (GNT), amphiregulin (AREG), and prostaglandin E2 (PGE2) stimulation of periovulatory gene mRNA levels occurs, at least in part, through the CCR2/MCP1 pathway, proposing the CCR2 receptor as a novel mediator of the ovulatory cascade in a feline model. For that purpose, feline cumulus-oocyte complexes (COCs) were cultured in the presence or absence of an EGFR inhibitor, recombinant chemokine MCP1, and gonadotropins [as an inducer of cumulus-oocyte expansion (C-OE), and oocyte maturation] to further assess the mRNA expression of periovulatory key genes, C-OE, oocyte nuclear maturation, and steroid hormone production. We observed that MCP1 was able to revert the inhibition of AREG mRNA expression by an EGFR inhibitor within the feline COC. In accordance, the confocal analysis showed that the GNT-stimulated hyaluronic acid (HA) synthesis, blocked by the EGFR inhibitor, was recovered by the addition of recombinant MCP1 in the C-OE culture media. Also, MCP1 was able to revert the inhibition of progesterone (P4) production by EGFR inhibitor in the C-OE culture media. Regarding oocyte nuclear maturation, recombinant MCP1 could also revert the inhibition triggered by the EGFR inhibitor, leading to a recovery in the percentage of metaphase II (MII)-stage oocytes. In conclusion, our results confirm the chemokine receptor CCR2 as a novel intermediate in the ovulatory cascade and demonstrate that the EGFR/AREG and the CCR2/MCP1 signaling pathways play critical roles in regulating feline C-OE and oocyte nuclear maturation, with CCR2/MCP1 signaling pathway being downstream EGFR/AREG pathway within the ovulatory cascade. |
| first_indexed | 2024-04-09T19:42:27Z |
| format | Article |
| id | doaj.art-c0cba209692c49d7b82ee3ed9993c304 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-09T19:42:27Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-c0cba209692c49d7b82ee3ed9993c3042023-04-04T05:03:46ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-04-011110.3389/fcell.2023.11618131161813Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascadeJ. G. Conte0J. G. Conte1M. L. Tellechea2B. Park3M. G. Ballerini4G. Jaita5G. Jaita6M. C. Peluffo7Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET—FEI—División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas (INBIOMED), Facultad de Medicina CONICET- Universidad de Buenos Aires, Buenos Aires, ArgentinaCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET—FEI—División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, ArgentinaBiostatistics Shared Resource, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United StatesCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET—FEI—División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, ArgentinaInstituto de Investigaciones Biomédicas (INBIOMED), Facultad de Medicina CONICET- Universidad de Buenos Aires, Buenos Aires, ArgentinaDepartamento de Biología Celular e Histología, Facultad de Medicina-Universidad de Buenos Aires Buenos, Buenos Aires, ArgentinaCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET—FEI—División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, ArgentinaThe epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte chemoattractant protein-1, MCP1) as novel mediators of the ovulatory cascade. Our previous results demonstrate that the gonadotropins (GNT), amphiregulin (AREG), and prostaglandin E2 (PGE2) stimulation of periovulatory gene mRNA levels occurs, at least in part, through the CCR2/MCP1 pathway, proposing the CCR2 receptor as a novel mediator of the ovulatory cascade in a feline model. For that purpose, feline cumulus-oocyte complexes (COCs) were cultured in the presence or absence of an EGFR inhibitor, recombinant chemokine MCP1, and gonadotropins [as an inducer of cumulus-oocyte expansion (C-OE), and oocyte maturation] to further assess the mRNA expression of periovulatory key genes, C-OE, oocyte nuclear maturation, and steroid hormone production. We observed that MCP1 was able to revert the inhibition of AREG mRNA expression by an EGFR inhibitor within the feline COC. In accordance, the confocal analysis showed that the GNT-stimulated hyaluronic acid (HA) synthesis, blocked by the EGFR inhibitor, was recovered by the addition of recombinant MCP1 in the C-OE culture media. Also, MCP1 was able to revert the inhibition of progesterone (P4) production by EGFR inhibitor in the C-OE culture media. Regarding oocyte nuclear maturation, recombinant MCP1 could also revert the inhibition triggered by the EGFR inhibitor, leading to a recovery in the percentage of metaphase II (MII)-stage oocytes. In conclusion, our results confirm the chemokine receptor CCR2 as a novel intermediate in the ovulatory cascade and demonstrate that the EGFR/AREG and the CCR2/MCP1 signaling pathways play critical roles in regulating feline C-OE and oocyte nuclear maturation, with CCR2/MCP1 signaling pathway being downstream EGFR/AREG pathway within the ovulatory cascade.https://www.frontiersin.org/articles/10.3389/fcell.2023.1161813/fullepidermal growth factor receptorC-C motif chemokine receptor 2monocyte chemoattractant protein 1cumulus-oocyte complexfelineovulatory cascade genes |
| spellingShingle | J. G. Conte J. G. Conte M. L. Tellechea B. Park M. G. Ballerini G. Jaita G. Jaita M. C. Peluffo Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade Frontiers in Cell and Developmental Biology epidermal growth factor receptor C-C motif chemokine receptor 2 monocyte chemoattractant protein 1 cumulus-oocyte complex feline ovulatory cascade genes |
| title | Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade |
| title_full | Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade |
| title_fullStr | Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade |
| title_full_unstemmed | Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade |
| title_short | Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade |
| title_sort | interaction between epidermal growth factor receptor and c c motif chemokine receptor 2 in the ovulatory cascade |
| topic | epidermal growth factor receptor C-C motif chemokine receptor 2 monocyte chemoattractant protein 1 cumulus-oocyte complex feline ovulatory cascade genes |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1161813/full |
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