Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice

Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether...

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Main Authors: Jia Li, Fangyue Zhou, Tuochen Zheng, Zezheng Pan, Xia Liang, Jian Huang, Liping Zheng, Yuehui Zheng
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2015-07-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/430144
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author Jia Li
Fangyue Zhou
Tuochen Zheng
Zezheng Pan
Xia Liang
Jian Huang
Liping Zheng
Yuehui Zheng
author_facet Jia Li
Fangyue Zhou
Tuochen Zheng
Zezheng Pan
Xia Liang
Jian Huang
Liping Zheng
Yuehui Zheng
author_sort Jia Li
collection DOAJ
description Background: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.
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spelling doaj.art-0b93de30e1df4b49a759c3d8aa5382dc2022-12-21T20:34:34ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013651712172410.1159/000430144430144Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in MiceJia LiFangyue ZhouTuochen ZhengZezheng PanXia LiangJian HuangLiping ZhengYuehui ZhengBackground: The Hippo signaling pathway plays fundamental roles in stem cell maintenance in a variety of tissues and has thus implications for stem cell biology. Key components of this recently discovered pathway have been shown to be associated with primordial follicle activation. However, whether the Hippo signaling pathway plays a role in the development of Ovarian Germline Stem Cells (OGSCs) during physiological and pathological ovarian aging in mice is unknown. Methods: Mice at the age of 7 days (7D), or of 2, 10, or 20 months (2M, 10M, 20M) and mice at 2M treated with TPT and CY/BUS drugs were selected as physiological and pathological ovarian aging models, respectively. Immunohistochemistry was used to assess the development of follicles, and the co-localization of genes characteristic of OGSCs with MST1, LATS2 and YAP1 was assessed by immunofluorescence, western blotting and real-time PCR methods. Results: The Hippo signal pathway and MVH/OCT4 genes were co-expressed in the mouse ovarian cortex. The level and co-localization of LATS2, MST1, MVH, and OCT4 were significantly decreased with increased age, but YAP1 was more prevalent in the mouse ovarian cortex of 2M mice than 7D mice and was not observed in 20M mice. Furthermore, YAP1, MVH, and OCT4 were gradually decreased after TPT and CY/BUS treatment, and LATS2 mRNA and protein up-regulation persisted in TPT- and CY/BUS-treated mice. However, the expression of MST1 was lower in the TPT and CY/BUS groups compared with the control group. In addition, pYAP1 protein showed the highest expression in the ovarian cortexes of 7D mice compared with 20M mice, and the value of pYAP1/YAP1 decreased from 7D to 20M. Moreover, pYAP1 decreased in the TPT- and CY/BUS-treated groups, but the value of pYAP1/YAP1 increased in these groups. Conclusion: Taken together, our results show that the Hippo signaling pathway is associated with the changes that take place in OGSCs during physiological and pathological ovarian aging in mice. Thus, the Hippo signaling pathway may be involved in the development schedule of OGSCs.http://www.karger.com/Article/FullText/430144Ovarian germline stem cellsHippo signalingOvarian agingMice
spellingShingle Jia Li
Fangyue Zhou
Tuochen Zheng
Zezheng Pan
Xia Liang
Jian Huang
Liping Zheng
Yuehui Zheng
Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice
Cellular Physiology and Biochemistry
Ovarian germline stem cells
Hippo signaling
Ovarian aging
Mice
title Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice
title_full Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice
title_fullStr Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice
title_full_unstemmed Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice
title_short Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway Association with Physiological and Pathological Ovarian Aging in Mice
title_sort ovarian germline stem cells ogscs and the hippo signaling pathway association with physiological and pathological ovarian aging in mice
topic Ovarian germline stem cells
Hippo signaling
Ovarian aging
Mice
url http://www.karger.com/Article/FullText/430144
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