PUBLICATION
Brain Derived Neurotrophic Factor Promotes Oocyte Maturation Through the TrkB-MAPk-PI3K Pathway in Zebrafish
- Authors
- Uju, C., Unniappan, S.
- ID
- ZDB-PUB-251118-6
- Date
- 2025
- Source
- Molecular and Cellular Endocrinology : 112703112703 (Journal)
- Registered Authors
- Keywords
- fish, follicle, growth factors, hormones, ovary, reproduction
- MeSH Terms
-
- Animals
- Azepines
- Benzamides
- Brain-Derived Neurotrophic Factor*/pharmacology
- Female
- Mitogen-Activated Protein Kinases*/metabolism
- Oocytes*/cytology
- Oocytes*/drug effects
- Oocytes*/metabolism
- Phosphatidylinositol 3-Kinases*/metabolism
- Phospholipase C gamma/metabolism
- Receptor, trkB*/antagonists & inhibitors
- Receptor, trkB*/metabolism
- Signal Transduction/drug effects
- Steroidogenic Factor 1/genetics
- Steroidogenic Factor 1/metabolism
- Vitellogenins/genetics
- Vitellogenins/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41248839 Full text @ Mol. Cell. Endocrinol.
Citation
Uju, C., Unniappan, S. (2025) Brain Derived Neurotrophic Factor Promotes Oocyte Maturation Through the TrkB-MAPk-PI3K Pathway in Zebrafish. Molecular and Cellular Endocrinology. :112703112703.
Abstract
Brain-derived neurotrophic factor (BDNF) was previously reported as a positive modulator of zebrafish reproduction, yet the mechanism of action of BDNF that elicits this function is unknown. We hypothesized that the pro-reproductive effects of BDNF in female zebrafish are mediated by TrkB signaling. In zebrafish liver (ZFL) cells, a TrkB antagonist (ANA-12) blocked the stimulatory effect of BDNF on transcript abundance of vitellogenin (vtg1, 2, 4, and 7) and steroidogenic factor 1 (sf-1). No changes were observed in hepatocyte nuclear factor 4 alpha, specificity protein 1, cAMP response element-binding protein 1a, or forkhead box L2. Blocking the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and phospholipase C gamma (PLC-γ) pathways significantly attenuated BDNF-induced upregulation of vtg and sf-1 transcripts. Total vtg protein was increased by BDNF, an effect that was blunted when TrkB, MAPK, PI3K, or PLC-γ were blocked. The estrogen receptor alpha (Esrα) fluorescence immunoreactivity in the ZFL cells was significantly reduced in the presence of ANA-12 compared to BDNF only. In the zebrafish follicles, BDNF-induced oocyte maturation was attenuated by TrkB, MAPK-, and PI3K inhibitors, but not a PLC-γ blocker. Similarly, the positive effects of BDNF on maturation-related genes 3β-hydroxysteroid dehydrogenase 2 enzyme (3bhsd2), cytochrome P450 family 17, hyaluronan synthase 2, luteinizing hormone receptor, and prostaglandin synthase 2 were significantly attenuated when TrkB, MAPK, or PI3K was blocked. PLC-γ inhibition prevented the BDNF-induced upregulation of 3bhsd1 in the oocytes. This study demonstrates that BDNF promotes vitellogenesis via the TrkB-MAPK/PI3K/PLC-γ signaling pathways. Meanwhile, BNDF enhances oocyte maturation through the TrkB-MAPK/PI3K pathways in female zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping