Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle through regulating p38 MAPK/p53/p21 pathway.

Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle through regulating p38 MAPK/p53/p21 pathway. Biol Reprod. 2017 Aug 28;: Authors: Chen MJ, Chou CH, Shun CT, Mao TL, Wen WF, Chen CD, Chen SU, Yang YS, Ho HN Abstract Iron is an essential nutrient that may exert toxic effects when it accumulates in tissues. Little is known regarding its effects on gonadal function. Both Fe2+ and Fe3+ could be released from iron deposition. We employed mouse non-luteinized granulosa cell for in vitro studies and human ovarian tissues for Prussian blue and immunohistochemical staining to identify the iron deposition and effect in vivo. After treatment with FeSO4-7H2O or FeCl3 in granulosa cell cultured with follicle stimulating hormone (FSH) for 48 hours, we found that Fe2+ significantly suppressed FSH-induced granulosa cell proliferation and arrested the cell cycle at the G2/M phase by cell proliferation assay and flow cytometry. Fe2+ significantly increased intracellular reactive oxygen species (ROS) and ferritin levels of mouse granulosa cells. The increases in p21 and p53 mRNA and protein expression facilitated by Fe2+ treatment in mouse granulosa cells were significantly suppressed by separate treatments with p53 siRNA and p38 mitogen-activated protein kinase (MAPK) inhibitors. A ROS inhibitor down-regulated Fe2+-induced increases in p38MAPK expression in mouse granulosa cells. Quantitative analysis of immunohistochemical s...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Tags: Biol Reprod Source Type: research