摘要
原文 | 英語 |
---|---|
頁(從 - 到) | 438-448 |
頁數 | 11 |
期刊 | Biology of Reproduction |
卷 | 97 |
發行號 | 3 |
DOIs | |
出版狀態 | 已發佈 - 一月 1 2017 |
對外發佈 | Yes |
指紋
ASJC Scopus subject areas
- Reproductive Medicine
- Cell Biology
引用此文
Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle through regulating p38 mitogen-activated protein kinase/p53/p21 pathway. / Chen, Mei Jou; Chou, Chia Hong; Shun, Chia Tung; Mao, Tsui Lien; Wen, Wen Fen; Chen, Chin Der; Chen, Shee Uan; Yang, Yu Shih; Ho, Hong Nerng.
於: Biology of Reproduction, 卷 97, 編號 3, 01.01.2017, p. 438-448.研究成果: 雜誌貢獻 › 文章
}
TY - JOUR
T1 - Iron suppresses ovarian granulosa cell proliferation and arrests cell cycle through regulating p38 mitogen-activated protein kinase/p53/p21 pathway
AU - Chen, Mei Jou
AU - Chou, Chia Hong
AU - Shun, Chia Tung
AU - Mao, Tsui Lien
AU - Wen, Wen Fen
AU - Chen, Chin Der
AU - Chen, Shee Uan
AU - Yang, Yu Shih
AU - Ho, Hong Nerng
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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 Fe 2+ and Fe 3+ could be released from iron deposition. We employed mouse nonluteinized 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 FeSO 4 -7H 2 O or FeCl 3 in granulosa cell cultured with folliclestimulating hormone (FSH) for 48 h, we found that Fe 2+ significantly suppressed FSH-induced granulosa cell proliferation and arrested the cell cycle at the G2/M phase by cell proliferation assay and flow cytometry. Fe 2+ significantly increased intracellular reactive oxygen species (ROS) and ferritin levels of mouse granulosa cells. The increases in p21 and p53 messenger RNA and protein expression facilitated by Fe 2+ treatment in mouse granulosa cells were significantly suppressed by separate treatments with p53 small interfering RNA and p38 mitogen-activated protein kinase (MAPK) inhibitors. An ROS inhibitor downregulated Fe 2+ -induced increases in p38MAPK expression in mouse granulosa cells. Quantitative analysis of immunohistochemical staining revealed that human ovarian tissue sections with positive Prussian blue staining had lower levels of proliferating cell nuclear antigen expression, but higher levels of p21, p53, and CDC25C expression than those with negative Prussian blue staining. Conclusively, Fe 2+ could directly arrest the cell cycle and inhibit granulosa cell proliferation by regulating the ROS-mediated p38MAPK/p53/p21 pathway. Therefore, iron can directly affect female gonadal function.
AB - 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 Fe 2+ and Fe 3+ could be released from iron deposition. We employed mouse nonluteinized 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 FeSO 4 -7H 2 O or FeCl 3 in granulosa cell cultured with folliclestimulating hormone (FSH) for 48 h, we found that Fe 2+ significantly suppressed FSH-induced granulosa cell proliferation and arrested the cell cycle at the G2/M phase by cell proliferation assay and flow cytometry. Fe 2+ significantly increased intracellular reactive oxygen species (ROS) and ferritin levels of mouse granulosa cells. The increases in p21 and p53 messenger RNA and protein expression facilitated by Fe 2+ treatment in mouse granulosa cells were significantly suppressed by separate treatments with p53 small interfering RNA and p38 mitogen-activated protein kinase (MAPK) inhibitors. An ROS inhibitor downregulated Fe 2+ -induced increases in p38MAPK expression in mouse granulosa cells. Quantitative analysis of immunohistochemical staining revealed that human ovarian tissue sections with positive Prussian blue staining had lower levels of proliferating cell nuclear antigen expression, but higher levels of p21, p53, and CDC25C expression than those with negative Prussian blue staining. Conclusively, Fe 2+ could directly arrest the cell cycle and inhibit granulosa cell proliferation by regulating the ROS-mediated p38MAPK/p53/p21 pathway. Therefore, iron can directly affect female gonadal function.
KW - Cell cycle
KW - Granulosa cells
KW - Iron
KW - Ovary
KW - Reactive oxygen specie
UR - http://www.scopus.com/inward/record.url?scp=85042087004&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042087004&partnerID=8YFLogxK
U2 - 10.1093/biolre/iox099
DO - 10.1093/biolre/iox099
M3 - Article
C2 - 29024968
AN - SCOPUS:85042087004
VL - 97
SP - 438
EP - 448
JO - Biology of Reproduction
JF - Biology of Reproduction
SN - 0006-3363
IS - 3
ER -