Novel direct effect of CCR2 receptor on follicle activation process
IntroductionThe regulation of primordial follicle activation is crucial for maintaining ovarian function, the duration of the reproductive phase, and fertility in women; therefore, we propose as our general objective to determine the physiological role of the chemokine receptor CCR2 within the folli...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1613270/full |
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| author | Yamila Gamaleri Delfina Sol Ferman Alison Ting Alison Ting Eduardo Raúl Dascal Alejandro Lomniczi Juan Pablo Jaworski Marina Cinthia Peluffo |
| author_facet | Yamila Gamaleri Delfina Sol Ferman Alison Ting Alison Ting Eduardo Raúl Dascal Alejandro Lomniczi Juan Pablo Jaworski Marina Cinthia Peluffo |
| author_sort | Yamila Gamaleri |
| collection | DOAJ |
| description | IntroductionThe regulation of primordial follicle activation is crucial for maintaining ovarian function, the duration of the reproductive phase, and fertility in women; therefore, we propose as our general objective to determine the physiological role of the chemokine receptor CCR2 within the follicular activation process.MethodsOvarian cortex fragments from adult domestic cats (Felis catus) were cultured under different experimental groups: control (media alone), CCR2 antagonist (1µM), and recombinant chemokine CC-motif ligand 2 (CCL2) at two concentrations (10 ng/ml and 100 ng/ml) for 4 h or 48 h. At the end of the culture, the fragments were collected for RNA extraction, cDNA synthesis, and quantitative real-time PCR (4 h) or fixed and processed for paraffin embedding (48 h) for hematoxylin and eosin staining or immunohistochemistry for Ki67, bromodeoxyuridine (BrdU) and AKTp.ResultsStimulation of CCR2 significantly increased the normalized mRNA expression of KIT, FOXO3 (10 ng/ml), and AKT (100 ng/ml) compared to the control (p<0,05). Moreover, there was a significant increase in the percentage of transitional follicles (and a decrease in primordial follicles), together with an increase in oocyte diameter compared with the control and the antagonist groups (p<0.05). Also, in the presence of CCL2, a higher proportion of transitional and primary follicles immunolabeled for BrdU and Ki67 (p<0.05), as well as intense AKTp staining in the nucleus and cytoplasm of oocyte and granulosa cells of primordial, transitional and primary follicles, were observed. On the contrary, a lower proportion of BrdU and Ki67-positive follicles were observed in the antagonist group (p < 0,05).ConclusionOur results show a direct effect of the chemokine CCL2 and a role of the CCR2/CCL2 system on the ovarian cortex, suggesting that the CCR2 receptor signaling in the ovarian cortex may regulate events critical for promoting the stimulation of the transition from primordial to primary follicles. |
| format | Article |
| id | doaj-art-9b4f790786b3411d9f9c05f527a4e3bc |
| institution | Matheson Library |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-9b4f790786b3411d9f9c05f527a4e3bc2025-08-01T04:10:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-08-011610.3389/fendo.2025.16132701613270Novel direct effect of CCR2 receptor on follicle activation processYamila Gamaleri0Delfina Sol Ferman1Alison Ting2Alison Ting3Eduardo Raúl Dascal4Alejandro Lomniczi5Juan Pablo Jaworski6Marina Cinthia Peluffo7Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) -CONICET–FEI–División de Endocrinología, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, ArgentinaCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) -CONICET–FEI–División de Endocrinología, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, ArgentinaExpanse Bio, LLC, Charleston, SC, United StatesDepartment of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Diego, San Diego, CA, United StatesCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) -CONICET–FEI–División de Endocrinología, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, ArgentinaDepartment of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, NS, CanadaNational Institute of Agricultural Technology-Instituto Nacional de tecnología agropecuaria (INTA)-CONICET, Castelar, ArgentinaCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE) -CONICET–FEI–División de Endocrinología, Hospital de Niños “Ricardo Gutiérrez”, Buenos Aires, ArgentinaIntroductionThe regulation of primordial follicle activation is crucial for maintaining ovarian function, the duration of the reproductive phase, and fertility in women; therefore, we propose as our general objective to determine the physiological role of the chemokine receptor CCR2 within the follicular activation process.MethodsOvarian cortex fragments from adult domestic cats (Felis catus) were cultured under different experimental groups: control (media alone), CCR2 antagonist (1µM), and recombinant chemokine CC-motif ligand 2 (CCL2) at two concentrations (10 ng/ml and 100 ng/ml) for 4 h or 48 h. At the end of the culture, the fragments were collected for RNA extraction, cDNA synthesis, and quantitative real-time PCR (4 h) or fixed and processed for paraffin embedding (48 h) for hematoxylin and eosin staining or immunohistochemistry for Ki67, bromodeoxyuridine (BrdU) and AKTp.ResultsStimulation of CCR2 significantly increased the normalized mRNA expression of KIT, FOXO3 (10 ng/ml), and AKT (100 ng/ml) compared to the control (p<0,05). Moreover, there was a significant increase in the percentage of transitional follicles (and a decrease in primordial follicles), together with an increase in oocyte diameter compared with the control and the antagonist groups (p<0.05). Also, in the presence of CCL2, a higher proportion of transitional and primary follicles immunolabeled for BrdU and Ki67 (p<0.05), as well as intense AKTp staining in the nucleus and cytoplasm of oocyte and granulosa cells of primordial, transitional and primary follicles, were observed. On the contrary, a lower proportion of BrdU and Ki67-positive follicles were observed in the antagonist group (p < 0,05).ConclusionOur results show a direct effect of the chemokine CCL2 and a role of the CCR2/CCL2 system on the ovarian cortex, suggesting that the CCR2 receptor signaling in the ovarian cortex may regulate events critical for promoting the stimulation of the transition from primordial to primary follicles.https://www.frontiersin.org/articles/10.3389/fendo.2025.1613270/fullfollicle activationCCR2MCP-1CCL2folliculogenesisfeline |
| spellingShingle | Yamila Gamaleri Delfina Sol Ferman Alison Ting Alison Ting Eduardo Raúl Dascal Alejandro Lomniczi Juan Pablo Jaworski Marina Cinthia Peluffo Novel direct effect of CCR2 receptor on follicle activation process Frontiers in Endocrinology follicle activation CCR2 MCP-1 CCL2 folliculogenesis feline |
| title | Novel direct effect of CCR2 receptor on follicle activation process |
| title_full | Novel direct effect of CCR2 receptor on follicle activation process |
| title_fullStr | Novel direct effect of CCR2 receptor on follicle activation process |
| title_full_unstemmed | Novel direct effect of CCR2 receptor on follicle activation process |
| title_short | Novel direct effect of CCR2 receptor on follicle activation process |
| title_sort | novel direct effect of ccr2 receptor on follicle activation process |
| topic | follicle activation CCR2 MCP-1 CCL2 folliculogenesis feline |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1613270/full |
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