Iorio, Giuseppe Gabriele (2025) ROLE OF THE OVARIAN NERVOUS SYSTEM IN THE PATHOPHYSIOLOGY OF FOLLICULOGENESIS: INSIGHTS FROM THE ENDOMETRIOSIS MODEL. [Tesi di dottorato]

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Abstract

The human ovary is a dynamic endocrine organ whose function and structure are tightly regulated by neuroendocrine and paracrine signals. Folliculogenesis involves both gonadotropin-dependent and -independent phases, yet the role of neural regulation in ovarian physiology remains incompletely understood. Endometriosis, a chronic estrogen-dependent inflammatory disease, is associated with pain, infertility and altered ovarian function, but the mechanisms linking neuropeptides, inflammation, and impaired follicular development are poorly defined. This prospective observational study evaluated calcitonin gene-related peptide (CGRP) levels in follicular fluid (FF) from 102 women undergoing fertility preservation, including 50 with endometriosis and 52 controls. FF samples were collected during oocyte retrieval, and CGRP concentrations were quantified using ELISA. Clinical, ultrasonographic and ovarian stimulation parameters were recorded. Results demonstrated significantly higher CGRP levels in the FF of women with endometriosis, while ovarian stimulation outcomes, including oocyte yield and maturation, were comparable between groups. These findings suggest that altered neuropeptidergic signaling may contribute to the local ovarian microenvironment in endometriosis, potentially influencing follicular dynamics independent of gonadotropin action. This study highlights the importance of ovarian innervation and neuropeptides in reproductive physiology and provides a foundation for further exploration of their role in endometriosis-associated infertility.

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