title: Hippo signaling pathway reveals a spatio-temporal correlation with the size of primordial follicle pool in mice.
abstract: BACKGROUND
  The Hippo signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms and regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Hippo signaling are expressed in mammalian ovaries, but the exact functions of this pathway in primordial follicle development remains unclear.
  
  
  METHODS
  To analyze the spatio-temporal correlation between the core component of Hippo pathway and the size of primordial follicle pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of mice primordial follicle in vitro.
  
  
  RESULTS
  Both the protein and mRNA expression of the MST1 and LATS2 were decreased significantly as mouse age increased (p < 0.05), however, the mRNA expression of them increased significantly in 16 m compared with 5 m as well as the protein expression of LATS2.The expression of YAP showed the opposite trend, and the significant protein expression of pYAP was increased before 1 m, after which no significant change was observed. Moreover, the ratio of pYAP/YAP decreased significantly. Culturing ovaries for 8 d in vitro resulted in the activation of primordial follicles in 3 d postnatal mice ovaries, and these developed into primary follicles with the expression of PCNA increasing significantly (p < 0.05). The mRNA and protein expression of MST and LATS decreased significantly (p < 0.05), and the expression of YAP increased significantly (p < 0.05, p < 0.01), whereas the ratio of pYAP/YAP decreased significantly (p < 0.05).
  
  
  CONCLUSIONS
  The above results reveal that the expression of the core components of Hippo pathway changed during mouse follicular development, especially before and after primordial follicle activation in vitro. The primordial follicle activation may be related to the significant decrease of the ratio of pYAP1/YAP1. In conclusion, Hippo signaling pathway expressed in mice ovaries and have spatio-temporal correlation with the size of primordial follicle pool.
authors: Medical Teaching Laboratory Center, Jiangxi Medical College, Nanchang University, Nanchang, China.
authors: Cheng
authors: C
authors: Xiang
authors: Jia
authors: J
authors: Li
authors: Liaoliao
authors: L
authors: Hu
authors: Jian
authors: J
authors: Huang
authors: Tao
authors: T
authors: Luo
authors: Zhisheng
authors: Z
authors: Zhong
authors: Yuehui
authors: Y
authors: Zheng
authors: Liping
authors: L
authors: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D000090683:Hippo Signaling Pathway; D006801:Humans; D051379:Mice; D006080:Ovarian Follicle / Q000254:growth & development* / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C490660:Stk4 protein, mouse; D000099317:Hippo Kinases; C522633:LATS2 protein, mouse