Open Access

ARTICLE

The Anti-Senescence Effect and Mechanism of 17β-Estradiol on Pelvic Organ Prolapse Derived Fibroblasts

Juan Cheng^1,#, Zhiwei Zhao^2,#, Ling Wang¹, Jirui Wen¹, Yali Miao^3,*, Jiang Wu^1,*

1 Department of Otolaryngology Head and Neck Surgery/Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, 610064, China
2 West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610064, China
3 Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, 610064, China

* Corresponding Authors: Yali Miao. Email: ; Jiang Wu. Email:
# These two authors contributed equally to this work and shared the first authorship

BIOCELL 2025, 49(2), 335-348. https://doi.org/10.32604/biocell.2025.059573

Received 11 October 2024; Accepted 13 January 2025; Issue published 28 February 2025

Abstract

Objectives: Recently, pre-/post-operative Local Estrogen Therapy (LET) has shown effectiveness in alleviating Pelvic Organ Prolapse (POP) symptoms in clinical therapy. However, there is a lack of scientific evidence to support these claims. Therefore, we aimed to explore the anti-senescence effects and mechanisms of 17β-estradiol (E2) on POP-derived fibroblasts. Methods: The primary fibroblast cells were isolated and cultured from the surgical samples of postmenopausal women clinically diagnosed with pelvic organ prolapse (POP) at stages III-IV (quantified using the POP-Q system) and without any other treatment within 6 months. (n = 12, age 50–75). Colorimetric Cell Counting Kit (CCK-8) assay and Senescence-Associated-β-Galactosidase (SA-β-Gal) staining were used to test the cell proliferative capacity and the senescence rate. Western blotting (WB) was used to detect the expression of Collagen Type I (COL-I), Collagen Type III (COL-III), Cyclin-dependent kinase 4 inhibitor A (p16^INK4a), Cyclin-dependent kinase inhibitor 1A (p21), Tumor Protein 53 (p53), Sirtuin 1 (SIRT-1) and Microtubule-associated protein 1A/1B-light chain 3-I/II (LC3-I/II) protein. A transmission Electron Microscope (TEM) was used to observe the ultrastructure of fibroblasts. Results: The results showed that E2 significantly promoted the proliferation of fibroblasts derived from POP and reduced the staining rate of SA-β-Gal. It markedly enhanced the extracellular matrix proteins COL-I and COL-III, accompanied by inhibition of the senescent maker p16INK4a. Additionally, our results improved the cells’ autophagy and metabolic activity. Additionally, our results indicate the anti-senescence mechanism of E2 through the mediated SIRT-1/p53/p21 axis pathway. Conclusion: We provide preliminary evidence for the anti-aging effects and mechanisms of E2 on POP, hoping to provide a theoretical basis for estrogen against POP senescence and guide the clinical application and local administration of estrogen in POP treatment.

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Keywords

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Supplementary Material

Supplementary Material File

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