ABSTRACT
Obese women with polycystic ovary syndrome (PCOS) often suffer from ovulation failure, which may be driven by granulosa cells (GCs) injury caused by increased levels of circulating oxidized low-density lipoprotein (ox-LDL) and luteinizing hormone (LH). PGC-1α may play an important role in this pathophysiological processes. However, the effect and the potential mechanism of PGC-1α on GCs injury evoked by obese PCOS is fully unclear. To investigate the protective effect and the potential mechanism of PGC-1α on GCs injury evoked by ox-LDL + LH stimulation. Patients with PCOS and women of normal reproductive age who undergoing egg retrievals and consenting for this research were collected. Those women were divided into normal-weight non-PCOS group, obese non-PCOS group, normal-weight PCOS group and obese PCOS group according to the body mass index (BMI) and PCOS diagnosis. Follicular fluid was collected and primary GCs were isolated. The levels of LH and ox-LDL in follicular fluid in the four groups were measured. And, the expressions of PGC-1α, cell apoptosis and ROS generation in primary GCs in the four groups were evaluated. After GCs from women of normal reproductive age at normal-weight pre-treated with adenovirus encoding PGC-1α (Ad-PGC-1α) prior to ox-LDL + LH treatment in vitro, the cell viability, apoptosis, apoptosis-related proteins expressions and ROS generation were evaluated by CCK-8 assay, AnnexinV/PI double staining, Western blot and H2DCF-DA staining, respectively. The expression of PGC-1α was significantly decreased, whereas the cell apoptosis and ROS generation were significantly increased in GCs of PCOS group, especially obese PCOS group. Our data also revealed that over-expression of PGC-1α in GCs from women of normal reproductive age at normal-weight markedly inhibited cell injury, ROS generation and p38 activation, accompanied by increased Bcl-2 expression, decreased Bax and cleaved caspase-3 expressions induced by ox-LDL + LH stimulation. Ox-LDL + LH-induced cell apoptosis was abrogated by attenuation of ROS generation or p38 activation. Attenuation of ROS generation reversed ox-LDL + LH-induced p38 activation, however, p38 inhibitors had an effect on ROS generation. Our findings suggested that PGC-1α protected against ox-LDL + LH-induced GCs injury through inhibiting cell apoptosis. And, the mechanism may be related to the inhibition of ROS-initiated p38 pathway. Our data indicated that PGC-1α may be a potential therapeutic target for obese PCOS.
Subject(s)
Granulosa Cells/pathology , Lipoproteins, LDL/adverse effects , Lipoproteins, LDL/metabolism , Luteinizing Hormone/adverse effects , Luteinizing Hormone/metabolism , MAP Kinase Signaling System/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/physiology , Polycystic Ovary Syndrome/etiology , Polycystic Ovary Syndrome/genetics , Reactive Oxygen Species/metabolism , Apoptosis/genetics , Cells, Cultured , Female , Gene Expression , Humans , Molecular Targeted Therapy , Polycystic Ovary Syndrome/therapyABSTRACT
OBJECTIVE: To evaluate the effectiveness and safety of uterine arterial embolization (UAE) in the management of symptomatic uterine myomas compared with myomectomy. METHODS: All clinical trials on UAE treating symptomatic uterine myomas indexed in PubMed and Chinese National Knowledge Infrastructure (CNKI) were reviewed using meta-analysis by Revman 4.1 software. The patients were classified into two groups, i.e., UAE trial group and control group. Intervention method in control group was surgery of uterine myomectomy. There were no differences between two groups in age, general physical status, and manifestation of uterine myoma. RESULTS: Six hundred and eighty patients with symptomatic uterine myoma in eight trials were included into this study according to selection criteria of Cochrane collaboration. Meta-analysis indicated that weight of every trial contributing to the study was related to its number of patients in direct ratio, but not related to quality scale of the trial. There were no statistical differences between these trials in evaluation criteria (P > 0.05). Relative risk (RR) between UAE patients and control group was 0.95, and 95% CI was 0.92 - 0.99. The success rate (92.3%) of UAE group was 95% of control group (96.7%), with a significant difference between them (P < 0.05). CONCLUSIONS: Surgical procedures to treat uterine myomas have more effective outcomes than UAE. Patients who select UAE procedure may have 95% opportunity to improve clinical symptoms and avoid some surgical risks, and also have a higher life quality in future, although this has to be testified by long term follow-up.
