ABSTRACT
CONTEXT: The high mobility group AT hook 2 (HMGA2) gene was previously identified in a genome-wide association study as a candidate risk gene that might be related to polycystic ovary syndrome (PCOS). Whether HMGA2 contributes to promoting granulosa cell (GC) proliferation in PCOS remains unknown. OBJECTIVE: We sought to determine whether HMGA2 is involved in the ovarian dysfunction of PCOS and in the mechanism of increased GC proliferation. PATIENTS AND CELLS: mRNA expression was analyzed in ovarian GCs from 96 women with PCOS and 58 healthy controls. Immortalized human GCs (KGN and SVOG cells) were used for the mechanism study. MAIN OUTCOME MEASURES: mRNA expression in ovarian GCs was measured using quantitative RT-PCR, and KGN cells were cultured for proliferation assays after overexpression or knockdown of target genes. Protein expression analysis, luciferase assays, and RNA binding protein immunoprecipitation assays were used to confirm the mechanism study. RESULTS: HMGA2 and IGF2 mRNA binding protein 2 (IMP2) were highly expressed in the GCs of women with PCOS, and the HMGA2/IMP2 pathway promoted GC proliferation. Cyclin D2 and SERPINE1 mRNA binding protein 1 were regulated by IMP2 and were highly expressed in women with PCOS. CONCLUSIONS: The HMGA2/IMP2 pathway was activated in women with PCOS and promoted the proliferation of GCs. This might provide new insights into the dysfunction of GCs in PCOS.
Subject(s)
Granulosa Cells/pathology , HMGA2 Protein/metabolism , Polycystic Ovary Syndrome/pathology , RNA-Binding Proteins/metabolism , Adult , Animals , Cell Line, Tumor , Cell Proliferation , China , Cyclin D2/metabolism , Female , Gene Expression Profiling , HEK293 Cells , HMGA2 Protein/genetics , Humans , Mice , Primary Cell Culture , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , Up-RegulationABSTRACT
OBJECTIVE: To evaluate the relationship between endometriosis fertility index (EFI) and pregnancies after laparoscopic surgery in endometriosis-associated infertility. METHODS: From Jan. 2005 to Jan. 2010, medical documents of 350 infertile patients due to endometriosis undergoing laparoscopic surgery were studied retrospectively. Pregnancy outcomes were followed up by telephone. EFI was calculated by history factors, least function score and some aspects of the revised American Fertility Society (r-AFS) endometriosis stage. The cumulative pregnancy rate was calculated and compared by Kaplan-Meier survival analysis. RESULTS: Within 3 years after surgery, the cumulative pregnancy rates among patients with EFI score 8, 9, 10 were 62.5%, 69.8% and 81.1%, respectively. There was no significant difference in pregnancy rates among those three groups of patients (P = 0.24). The cumulative pregnancy rates among patients with EFI score 5, 6, 7 were 49.8%, 43.9% and 41.6%, respectively, which did not reach statistical difference (P = 0.83). The cumulative pregnancy rates of EFI score 8 - 10 was significantly higher than that of EFI score 5 - 7 (71.8% vs. 44.4%, P = 0.000). The patients with EFI score 0 - 4 was quite small with only 33 cases, among which 15 cases were pregnant. CONCLUSIONS: There is relationship between EFI and pregnancy in patients with endometriosis-associated infertility. EFI is meaningful to guide post-surgical treatment.
