P66 | FROM INNERVATION TO STEROIDOGENIC DEFECT: IMPLICATIONS OF CGRP IN THE PATHOPHYSIOLOGY OF POLYCYSTIC OVARY SYNDROME

L. Sallicandro¹, R. Gentile², B. Filová³, S. Polakovičová³, A. Biagini¹, F. Ballarino⁴, D. Del Bianco⁴, I. Varga⁵, A. Malvasi⁶, B. Fioretti² | ¹Department of Medicine and Surgery, University of Perugia, Perugia, Italy; ²Department of Chemistry, Biology and Biotechnologies, University of Perugia, Italy; ³Department of Histology and Embriology, Comenius University, Bratislava, Slovakia; ⁴Department of Chemistry, Biology and Biotechnologies, University of Perugia, Italy; ⁵Department of Histology and Embriology, Comenius University, Bratislava, Slovakia; ⁶Department of Biomedical Sciences and Human Oncology, Obstetrics and Gynecology Unit, University of Bari Aldo Moro, Bari, Italy

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder affecting up to 20% of women of reproductive age. It is characterized by hyperandrogenism, menstrual irregularities, anovulation, and metabolic disturbances, including insulin resistance and increased cardiometabolic risk¹. Although its pathogenesis remains unclear, recent studies suggest a potential role for neuropeptides in modulating ovarian function². This study aims to investigate the presence of calcitonin gene related peptide (CGRP), a 37-amino-acid neuropeptide involved in vasodilation, nociceptive signaling, and modulation of the inflammatory response³, within the ovary and follicular fluid of women with PCOS. CGRP levels were quantified in follicular fluid from PCOS (n=27) and non-PCOS (n=27) women, showing significantly higher concentrations in the PCOS group (p<0.05). Immunohistochemistry analyses revealed intense CGRP immunoreactivity surrounding preantral follicles in PCOS ovaries, particularly around the theca cell layer. In contrast, non-PCOS samples exhibited weaker CGRP expression. This differential pattern suggests a possible involvement of CGRP in early follicular development. The altered follicular microenvironment in PCOS may permit the accumulation of small neuropeptides like CGRP, which could exert autocrine/paracrine effects on follicular cells, influencing both development and steroidogenesis⁴. To further investigate this hypothesis, we assessed the effects of CGRP on cell viability, mitochondrial and steroidogenic activity in primary h-GCs. These findings suggest that CGRP may contribute to the dysregulation of follicular development observed in PCOS. A better understanding of its role could offer new insights for the development of targeted therapies aimed at restoring ovarian function in affected women.