JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):122
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263756

P-110. Functional Reprogramming of Endometrial Stromal Cells induced by Angiotensin II

Stephanie Lins Silveira¹, Letícia Quandt¹, Pamela Zanon¹, Maria Eduarda Leite Simões¹, Amanda Wink Santos¹, Eduardo Pandolfi Passos¹, Paula Barros Terraciano¹, Markus Berger¹

¹ Hospital de Clínicas de Porto Alegre - Porto Alegre - Rio Grande do Sul - Brasil

Objective: Endometriosis is a chronic, estrogen-dependent inflammatory condition that affects approximately 10% of reproductive-age women and is a major cause of infertility. The disorder is characterized by abnormal cellular behaviors, including enhanced migration, matrix emodeling, and sustained inflammation, which support the ectopic survival of endometrial tissue. Angiotensin II (Ang II), a key peptide of the renin–angiotensin system, has been implicated in these processes, but its specific molecular effects on human endometrial stromal cells (hESCs) remain poorly defined.
Methods: Primary hESCs were obtained from patients undergoing IVF procedures in the Reproduction Center of our institution (ethical approval number 2023-0258). The cells were treated with 10 nM Ang II and analyzed using high-resolution mass spectrometry to characterize global proteomic changes. Bioinformatic analyses were applied to identify enriched pathways and signaling networks. In parallel, dose–response assays (1–10 nM Ang II) were performed to evaluate cell proliferation and morphological alterations over a 6-day period.
Results: Ang II induced broad proteomic remodeling in hESCs, with enrichment of pathways related to cytoskeletal dynamics, focal adhesion, integrin signaling, inflammatory activation, and oxidative stress adaptation—molecular programs commonly associated with endometriosis pathophysiology. These alterations were reflected in phenotypic outcomes: Ang II treatment promoted a dose-dependent increase in cell proliferation and significantly reduced population doubling time. Morphometric analyses revealed time-dependent increases in cell area, length, and perimeter, along with a progressive reduction in circularity. Notably, an inverse correlation between cell length and circularity over time suggested the acquisition of a polarized, migratory morphology associated with lamellipodia formation and pseudopod extension.
Conclusion: Our findings demonstrate that Ang II promotes a coordinated molecular and morphological shift in hESCs, fostering a pro-invasive and pro-inflammatory phenotype aligned with key mechanisms of endometriosis progression. These results reinforce the potential of targeting the Ang II/AT1R axis and its downstream signaling pathways as part of non-hormonal therapeutic strategies for endometriosis.