Journal Article

Progesterone and IL-6 Expression Are Modulated by Follicular Fluid in Granulosa Cell Cultures

Brun, Paola, Frison, Carolina, Sabbadin, Chiara, Andrisani, Alessandra, Gullo, Giuseppe, Ambrosini, Guido, Marin, Loris, Armanini, Decio, Radu, Claudia Maria, Ragazzi, Eugenio, Bordin, Luciana

2025

Overview

Endometriosis (ENDO) and poor ovarian response (POR) represent challenging conditions in assisted reproduction. Both, associated with altered follicular fluid (FF) composition, specifically impact on granulosa cell (GC) function in an incompletely understood way. GCs from male factor (MF, n = 30), ENDO (n = 38), and POR (n = 27) patients were cultured in media supplemented with FF from each group (FF-MF, FF-ENDO, FF-POR). Proliferation, morphology, and secretory activity (cortisol, estradiol, progesterone, IL-6) were assessed. GC proliferation depended primarily on FF origin, being highest with FF-ENDO, intermediate with FF-POR, and lowest with FF-MF. Morphological analysis revealed enrichment of muscle-like and fibroblast-like morphologies under FF-ENDO and FF-POR, suggestive of dysregulated luteinization and extracellular matrix remodeling. Secretory activity reflected a complex interplay between GC origin and FF type: IL-6 was strongly induced by FF-MF and FF-POR but consistently suppressed by FF-ENDO; cortisol and estradiol were generally consumed, while progesterone synthesis was largely confined to MF-GCs, with only variable induction in ENDO-GCs exposed to FF-POR. These findings indicate that pathological FF milieus reprogram GC behavior in distinct ways, with potential consequences for luteal function and oocyte competence. Identifying the molecular mediators of these alterations may guide tailored strategies to improve ART outcomes in ENDO and POR patients.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: 17β-Estradiol / Adult / Cell Proliferation / Cells, Cultured / Corticosteroids / Cortisol / Cytokines / Endometriosis / Endometriosis - metabolism / Endometriosis - pathology / Estradiol / Estradiol - metabolism / Extracellular matrix / Female / Follicles / Follicular fluid / Follicular Fluid - metabolism / Ganirelix / granulosa cells / Granulosa Cells - cytology / Granulosa Cells - metabolism / Hormones / Humans / In vitro fertilization / Infertility / Interleukin 6 / Interleukin-6 - genetics / Interleukin-6 - metabolism / Ovaries / Ovulation / Patients / poor ovarian responder / Progesterone / Progesterone - metabolism / Reproductive technologies