title: Sohlh2 inhibits the apoptosis of mouse primordial follicle oocytes via C-kit/PI3K/Akt/Foxo3a signalling pathway.
abstract: We previously reported that bone morphogenetic protein 4/drosophila mothers against decapentaplegic protein (BMP4/Smad) signalling pathway initiated primordial follicle growth and prevented oocyte apoptosis via up-regulation of Sohlh2 and receptor for kit ligand (c-kit). The mechanism underlying this process was not fully elucidated. In the present study, primary oocyte cultures were established from ovaries of 3-day-old female mouse pups by two-step enzyme digestion. Cultures were divided into Sohlh2 small interference RNA (SiRNA) group, negative SiRNA group, Sohlh2 overexpression plasmid group and pCAG-puro group. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay was carried out to detect the oocyte apoptosis; immunocytochemical staining and quantitative real time-polymerase chain reaction detected the expression of c-kit and Forkhead box O3a (Foxo3a); Western blot was performed to detect the expression of Sohlh2, C-kit, saerine/threonine kinases (Akt1) and Foxo3a. The results showed that Sohlh2 inhibited oocyte apoptosis and upregulated c-kit expression; Sohlh2 decreased the endonuclear Foxo3a via the upregulation of phosphorylated Akt1 (P-Akt1) and phosphorylated Foxo3a (P-Foxo3a) but not total Akt1 (T-Akt1) or total Foxo3a (T-Foxo3a); Sohlh2 increased P-Akt1 but not T-Akt1; the PI3K (phosphotidylinsitol-3-kinase) inhibitor LY294002 ameliorated the role of Sohlh2 on phosphorylation of Akt1 and Foxo3a. Sohlh2 may inhibit oocyte apoptosis via c-kit/PI3K/Akt/Foxo3a signalling pathway.
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Haiyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Ji
authors.affiliation: Department of Morphology Laboratory, School of Medicine, Shandong University, Jinan, China.
authors.forename: Lujun
authors.initials: L
authors.lastname: Bing
authors.affiliation: Key Laboratory of the Ministry of Education for Experimental Teratology, Department of Histology and Embryology, School of Medicine, Shandong University, Jinan, China. Electronic address: haojing@sdu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002867:Chromones / Q000494:pharmacology; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002867:Chromones; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019009:Proto-Oncogene Proteins c-kit; C474033:FoxO3 protein, mouse; C515516:Sohlh2 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: C-kit/PI3K/Akt/Foxo3a; Sohlh2; TUNEL; apoptosis; mouse; oocyte