Anti-apoptotic action of stem cell factor on oocytes in primordial follicles and its signal transduction
Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti‐apoptotic action of SCF and...
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Published in | Molecular reproduction and development Vol. 70; no. 1; pp. 82 - 90 |
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Language | English |
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Abstract | Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti‐apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3′‐end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti‐apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis‐related gene products, the Bcl‐2 family proteins, in response to SCF treatment were also investigated. While SCF up‐regulated the expression of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL, it did the opposite to the pro‐apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl‐xL and Bax but not on Bcl‐2. Therefore, it seemed that SCF initiated an anti‐apoptotic signal starting from its membrane receptor c‐kit to Bcl‐2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles. Mol. Reprod. Dev. 70: 82–90, 2004. © 2004 Wiley‐Liss, Inc. |
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AbstractList | Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti‐apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3′‐end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti‐apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis‐related gene products, the Bcl‐2 family proteins, in response to SCF treatment were also investigated. While SCF up‐regulated the expression of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL, it did the opposite to the pro‐apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl‐xL and Bax but not on Bcl‐2. Therefore, it seemed that SCF initiated an anti‐apoptotic signal starting from its membrane receptor c‐kit to Bcl‐2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles. Mol. Reprod. Dev. 70: 82–90, 2004. © 2004 Wiley‐Liss, Inc. Abstract Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti‐apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3′‐end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti‐apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis‐related gene products, the Bcl‐2 family proteins, in response to SCF treatment were also investigated. While SCF up‐regulated the expression of the anti‐apoptotic proteins Bcl‐2 and Bcl‐xL, it did the opposite to the pro‐apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl‐xL and Bax but not on Bcl‐2. Therefore, it seemed that SCF initiated an anti‐apoptotic signal starting from its membrane receptor c‐kit to Bcl‐2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles. Mol. Reprod. Dev. 70: 82–90, 2004. © 2004 Wiley‐Liss, Inc. Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the underlying mechanism remains largely unknown. By using cultured ovaries that are rich in primordial follicles, the anti-apoptotic action of SCF and the potential signal transduction pathways were investigated. The apoptosis was evaluated by means of in situ 3'-end labeling. The expressions of proteins were analyzed with immunohistochemistry and Western blot. The data showed that SCF significantly prevented oocytes from apoptosis in the cultured organs. Addition of a specific pharmacological inhibitor of PI3K abolished the anti-apoptotic action of SCF while that of a MEK inhibitor did not. The phosphorylation of two mitogen activated protein kinases (MAPKs) (p42 and p44) and AKT, the respective substrates of MEK and PI3K, were enhanced by SCF treatment. Not surprisingly, the MAPK activation occurred only in theca cells. The expressions of apoptosis-related gene products, the Bcl-2 family proteins, in response to SCF treatment were also investigated. While SCF up-regulated the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, it did the opposite to the pro-apoptotic factor Bax. The PI3K inhibitor reversed the regulation of SCF on Bcl-xL and Bax but not on Bcl-2. Therefore, it seemed that SCF initiated an anti-apoptotic signal starting from its membrane receptor c-kit to Bcl-2 family members through PI3K/AKT and other signaling cascades in the oocytes of primordial follicles. |
Author | Yu, Fu-Qing Wei, Peng Hu, Zhao-Yuan Liu, Yi-Xun Han, Chun-Sheng Jin, Xuan |
Author_xml | – sequence: 1 givenname: Xuan surname: Jin fullname: Jin, Xuan organization: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China – sequence: 2 givenname: Chun-Sheng surname: Han fullname: Han, Chun-Sheng organization: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China – sequence: 3 givenname: Fu-Qing surname: Yu fullname: Yu, Fu-Qing organization: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China – sequence: 4 givenname: Peng surname: Wei fullname: Wei, Peng organization: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China – sequence: 5 givenname: Zhao-Yuan surname: Hu fullname: Hu, Zhao-Yuan organization: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China – sequence: 6 givenname: Yi-Xun surname: Liu fullname: Liu, Yi-Xun email: liuyx@panda.ioz.ac.cn organization: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China |
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Keywords | Rat Folliculogenesis Rodentia signaling pathway Germinal cell In vitro Ovary Signal transduction Vertebrata Mammalia Female genital system Mast cell growth factor Oocyte Apoptosis |
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Snippet | Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However, the... Abstract Stem cell factor (SCF) is essential for the development of primordial follicles. One of its functions is to prevent oocytes from apoptosis. However,... |
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SubjectTerms | Animals apoptosis Apoptosis - drug effects Apoptosis - physiology Biological and medical sciences Female Fundamental and applied biological sciences. Psychology Hormone metabolism and regulation Intracellular Signaling Peptides and Proteins - pharmacology Mammalian female genital system Oocytes - chemistry Oocytes - drug effects Organ Culture Techniques Ovarian Follicle - chemistry Ovarian Follicle - drug effects ovary Phosphatidylinositol 3-Kinases - antagonists & inhibitors Phosphatidylinositol 3-Kinases - metabolism Phosphatidylinositol 3-Kinases - physiology Phosphorylation Protein-Serine-Threonine Kinases - analysis Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Proto-Oncogene Proteins c-bcl-2 - analysis Proto-Oncogene Proteins c-bcl-2 - metabolism Rats Signal Transduction - drug effects Signal Transduction - physiology signaling pathway Stem Cell Factor - pharmacology Stem Cell Factor - physiology Vertebrates: reproduction |
Title | Anti-apoptotic action of stem cell factor on oocytes in primordial follicles and its signal transduction |
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