期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 15, 页码 -出版社
MDPI
DOI: 10.3390/ijms22158216
关键词
miR-210; VEGFA; HIF-1 alpha; ovulation; corpus luteum
资金
- German-Israeli Foundation for Scientific Research and Development (GIF) [I-1417-201.2/2017]
- Robert H. Smith Faculty of Agriculture, Food, and Environment Research Fund for International Cooperation scholarship
- Society for Biology of Reproduction in Poland
Granulosa-lutein cells (GLCs) from PCOS women exhibit reduced levels of HIF-1 alpha and EDN2, with microRNA-210 playing a key role in regulating this process. The disrupted hypoxic response in the GLCs of periovulatory follicles in PCOS may contribute to ovulation failure and reduced fertility in this syndrome.
Granulosa-lutein cells (GLCs) from PCOS women display reduced HIF-1 alpha and EDN2 levels, suggesting their role in PCOS etiology. Here, we investigated the mechanisms involved in aberrant EDN2 expression in PCOS, and its association with HIF-1 alpha. Various HIF-1 alpha-dependent factors were studied in GLCs from PCOS and compared to normally ovulating women. MicroRNA-210 (miR-210), its target genes (SDHD and GPD1L), and HIF-1 alpha-responsive genes (EDN2 and VEGFA) differed in GLCs from PCOS, compared with those of healthy women. Levels of miR-210-designated hypoxiamiR-and EDN2 were reduced in the PCOS GLCs; concomitantly, GPD1L and SDHD levels were elevated. Cultured GLCs retained low EDN2 expression and had low HIF-1 alpha levels, providing evidence for a disrupted hypoxic response in the PCOS GLCs. However, VEGFA expression was elevated in these cells. Next, miR-210 levels were manipulated. miR-210-mimic stimulated EDN2 twice as much as the miR-NC-transfected cells, whereas miR-210-inhibitor diminished EDN2, emphasizing the importance of hypoxiamiR for EDN2 induction. Intriguingly, VEGFA transcripts were reduced by both miR-210-mimic and -inhibitor, demonstrating that EDN2 and VEGFA are distinctly regulated. Disrupted hypoxic response in the GLCs of periovulatory follicles in PCOS women may play a role in ovulation failure, and in the reduced fertility prevalent in this syndrome.
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