Investigating the impact of local inflammation on granulosa cells and follicular development in women with ovarian endometriosis
Intrafollicular tumor necrosis factor-a might activate nuclear factor kB signaling pathway in endometriosis granulosa cells, which might impair telomerase activity and oocyte quality.
Volume 112, Issue 5, Pages 882–891.e1
Ying Li, M.D., Ruiqi Li, Ph.D., Nengyong Ouyang, B.D., Kailing Dai, B.D., Ping Yuan, Ph.D., Lingyan Zheng, M.D., Wenjun Wang, Ph.D.
To investigate the possible impact of local inflammation on granulosa cells (GCs) and follicular development in endometriosis patients.
Prospective study with related paired design.
Reproductive medicine center.
A total of 80 endometriosis patients and 104 controls, with cultured GCs collected from control participants younger than 35 years.
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.
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-κBʹ = −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).
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.