Investigating the impact of local inflammation on granulosa cells and follicular development in women with ovarian endometriosis
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This study investigated the effects of local inflammation associated with ovarian endometriosis on granulosa cells and the development of ovarian follicles in women.
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Abstract
OBJECTIVE: To investigate the possible impact of local inflammation on granulosa cells (GCs) and follicular development in endometriosis patients.
DESIGN: Prospective study with related paired design.
SETTING: Reproductive medicine center.
PATIENT(S): A total of 80 endometriosis patients and 104 controls, with cultured GCs collected from control participants younger than 35 years.
INTERVENTION(S): Tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB) inhibitor.
MAIN OUTCOME MEASURE(S): Intrafollicular concentrations of cytokines measured with ELISA, NF-κB binding levels with electrophoretic mobility shift assay (EMSA), and telomerase activity (TA) with quantitative-telomeric repeat amplification protocol (Q-TRAP) assay, and protein and mRNA expression with Western blot and polymerase chain reaction analyses, respectively.
RESULT(S): Patients with endometriosis exhibited a statistically significantly lower antral follicle count (11.48 ± 8.11 vs. 15.68 ± 8.56), lower number of retrieved oocytes (8.28 ± 6.69 vs. 10.87 ± 6.26), and lower number of mature oocytes (6.67 ± 6.09 vs. 8.53 ± 5.69). The GCs from endometriosis patients showed higher NF-κB binding activity and increased expression of inhibitor of NF-κB kinase subunit β (IKKβ, 2.743-fold) and NF-κB inhibitor α (IκBα, 5.017-fold). Their NF-κB p65 expression was negatively associated with mature oocytes (bNF-κB' = -0.304, R2 = 0.195, R = 0.442) but positively associated with intrafollicular TNF-α (r = 0.37); TA showed a negative relationship with NF-κB binding levels (r = -0.667). Tumor necrosis factor-α induced expression of IκBα (5.408-fold) and NF-κB p65 (1.400-fold) but lowered human telomerase reverse transcriptase (hTERT) and TA levels (0.0009 vs. 0.5619) in cultured GCs. However, inhibiting NF-κB obviously increased hTERT expression (1.988-fold).
CONCLUSION(S): Endometriosis showed activated NF-κB pathways in GCs, which might negatively affect TA and oocyte quality. Intrafollicular TNF-α might down-regulate TA and hTERT via NF-κB pathway, but further studies are required.
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Cited by (26)
- The biology and clinical aspects of female infertility 2026
- Molecular Insights Into Endometriosis for Early Detection and Therapeutic Targets 2026
- The biology and clinical aspects of female infertility 2026
- Single-cell transcriptomic atlas of ovarian endometriosis patient's follicular fluid: unraveling novel insights into abnormal follicular development 2026
- Precision Therapeutic and Preventive Molecular Strategies for Endometriosis-Associated Infertility 2025
- Methyl 3,4-dihydroxybenzoate alleviates oxidative damage in granulosa cells by activating Nrf2 antioxidant pathway 2024
- Endometriosis and the Role of Pro-Inflammatory and Anti-Inflammatory Cytokines in Pathophysiology: A Narrative Review of the Literature 2024
- Impact of the Endometriomas on the Ovarian Follicles 2024
- Platelets as key cells in endometriosis patients: insights from small extracellular vesicles in peritoneal fluid and endometriotic lesions analysis 2024
- MiR-19b-3p inhibits cell viability and proliferation and promotes apoptosis by targeting IGF1 in KGN cells 2023
- Diminished Ovarian Reserve in Endometriosis: Insights from In Vitro, In Vivo, and Human Studies-A Systematic Review 2023
- A Validated Model for Individualized Prediction of Live Birth in Patients With Adenomyosis Undergoing Frozen-Thawed Embryo Transfer 2022
- Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis 2022
- The cytokine profiles in follicular fluid and reproductive outcomes in women with endometriosis 2022
- Additional file 2 of Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway 2021
- Construction of Competing Endogenous RNA Networks Incorporating Transcription Factors to Reveal Differences in Granulosa Cells from Patients with Endometriosis 2021
- Ovarian endometriosis and fertility preservation problem 2021
- Additional file 1 of Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway 2021
- Additional file 1 of Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway 2021
- Additional file 2 of Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway 2021
- The impact of phthalate on reproductive function in women with endometriosis 2021
- Overexpressed MPS-1 contributes to endometrioma development through the NF-κB signaling pathway 2021
- How Can We Optimize the Granulose Cell Function of Oocytes from an Endometriosis Patient to Improve the Reproductive Outcomes-A Short Communication? 2020
- How Can We Optimize the Granulose Cell Function of Oocytes from an Endometriosis Patient to Improve the Reproductive Outcomes-A Short Communication? 2020
- Circular RNA expression profiling and bioinformatic analysis of cumulus cells in endometriosis infertility patients 2020
- Lifting the endometrioma veil on granulosa cells 2019
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