Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Reproduction

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1613270

This article is part of the Research TopicEndocrine Regulation of Ovarian Follicle Development and Oocyte Maturation: Molecular Mechanisms and Functional InsightsView all 4 articles

Novel direct effect of CCR2 receptor on follicle activation process

Provisionally accepted
  • 1CONICET Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), Buenos Aires, Argentina
  • 2Gaia Life, San Diego, United States
  • 3Department of Obstetrics, Gynecology and Reproductive Sciences, School of Medicine, University of California, San Diego, La Jolla, California, United States
  • 4Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada., Halifax, Canada
  • 5INTA (National Institute of Agricultural Technology-Instituto Nacional de tecnología agropecuaria)-CONICET, Argentina., Buenos Aires, Argentina

The final, formatted version of the article will be published soon.

The 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.Methods: Ovarian 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.Results: Stimulation 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).Our 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.

Keywords: follicle activation1, CCR22, MCP-13, CCL24, folliculogenesis5, feline6

Received: 16 Apr 2025; Accepted: 14 Jul 2025.

Copyright: © 2025 Gamaleri, Ferman, Ting, Dascal, Lomniczi, Jaworski and Peluffo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Marina C. Peluffo, CONICET Centro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), Buenos Aires, Argentina

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.