Wnt/β-catenin signaling regulates follicular development by modulating the expression of Foxo3a signaling components.
Wnt signaling is an evolutionarily conserved pathway that regulates cell proliferation, differentiation and apoptosis. To investigate the possible role of Wnt signaling in the regulation of ovarian follicular development, secondary follicles were isolated and cultured in vitro in the presence or absence of its activator (LiCl or Wnt3a) or inhibitor (IWR-1). We have demonstrated that activation of β-catenin signals by activators dramatically suppressed follicular development by increasing granulosa cell apoptosis and inhibiting follicle steroidogenesis. In contrast, inhibition of Wnt signaling by IWR-1 was observed with better developed follicles and increased steroidogenesis. Further studies have shown that the transcription factor Forkhead box O3a (Foxo3a) and its downstream target molecules were modulated by the activators or the inhibitor. These findings provide evidence that Wnt signaling might negatively regulate follicular development potentially through Foxo3a signaling components.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
Lei
L
Li
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
Shao-Yang
SY
Ji
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
Jun-Ling
JL
Yang
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
Xi-Xia
XX
Li
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
Jun
J
Zhang
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Graduate School of the Chinese Academy of Sciences, Beijing 100049, China.
Yang
Y
Zhang
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Zhao-Yuan
ZY
Hu
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: liuyx@ioz.ac.cn.
Yi-Xun
YX
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007094:Imides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D061251:Primary Cell Culture; D011804:Quinolines / Q000494:pharmacology; D015398:Signal Transduction; D013256:Steroids / Q000096:biosynthesis; D060509:Wnt3A Protein / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
C495267:CTNNB1 protein, mouse; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; C585534:IWR-1 compound; D007094:Imides; D011804:Quinolines; D013256:Steroids; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D051176:beta Catenin; D018021:Lithium Chloride
3β-HSD; 3β-hydroxysteroid dehydrogenase; APC; CTNNB1; CYP11A1; CYP19A1; DMSO; FBS; FZD; Follicle culture; Forkhead box O; Foxo; Foxo3a; GSK3β; HMG-domain; IWR; IWR-1; LRP; LiCl; P450 cholesterol side chain cleavage; PUMA; StAR; T-cell factor/lymphoid enhancer-binding protein; TCF/LEF; TUNEL; Wnt; Wnt/β-catenin signaling; Wnt3a; adenomatosis polyposis coli; cytochrome P450 aromatase; dimethylsulfoxide; fetal bovine serum; frizzled; glycogen synthase kinase 3β; high mobility group domain; inhibitors of Wnt response; lipoprotein receptor-related proteins; p53-upregulated modulator of apoptosis; steroidogenic acute regulatory protein; terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling; wingless-type mouse mammary tumor virus integration site family; β-catenin