Anti-apoptotic action of stem cell factor on oocytes in primordial follicles and its signal transduction

• Published in: Molecular reproduction and development Vol. 70; no. 1; pp. 82 - 90
• Main Authors: Jin, Xuan, Han, Chun-Sheng, Yu, Fu-Qing, Wei, Peng, Hu, Zhao-Yuan, Liu, Yi-Xun
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2005; Wiley-Liss
• Subjects: 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; Rat; Folliculogenesis; Rodentia; signaling pathway; Germinal cell; In vitro; Ovary; Signal transduction; Vertebrata; Mammalia; Female genital system; Mast cell growth factor; Oocyte; Apoptosis
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.20142

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.