PUBLICATION

Role of natriuretic peptide receptor 2-mediated signaling in meiotic arrest of zebrafish oocytes and its estrogen regulation through G protein-coupled estrogen receptor (Gper)

Authors
Pang, Y., Thomas, P.
ID
ZDB-PUB-180327-3
Date
2018
Source
General and comparative endocrinology   265: 180-187 (Journal)
Registered Authors
Keywords
Meiotic arrest, Natriuretic peptide receptor 2, NPR2, Natriuretic peptide type C, NPPC, Phosphodiesterase, PDE, Zebrafish oocyte maturation, cGMP
MeSH Terms
  • Animals
  • Cell Cycle Checkpoints/drug effects*
  • Estrogens/pharmacology*
  • Female
  • Gene Expression Regulation/drug effects
  • Meiosis*/drug effects
  • Natriuretic Peptide, C-Type/genetics
  • Natriuretic Peptide, C-Type/metabolism
  • Oocytes/cytology*
  • Oocytes/drug effects
  • Oocytes/metabolism
  • Oogenesis/drug effects
  • Ovarian Follicle/cytology
  • Phosphodiesterase Inhibitors/pharmacology
  • Quinolones/pharmacology
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Atrial Natriuretic Factor/genetics
  • Receptors, Atrial Natriuretic Factor/metabolism*
  • Receptors, G-Protein-Coupled/metabolism*
  • Rolipram/pharmacology
  • Signal Transduction*/drug effects
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
PubMed
29574150 Full text @ Gen. Comp. Endocrinol.
Abstract
Natriuretic peptide type C (NPPC) and its receptor, natriuretic peptide receptor 2 (NPR2), have essential roles in maintaining meiotic arrest of oocytes in several mammalian species. However, it is not known if a similar mechanism exists in non-mammalian vertebrates. Using zebrafish as a model, we show that Nppc is expressed in ovarian follicle cells, whereas Npr2 is mainly detected in oocytes. Treatment of intact and defolliculated oocytes with 100 nM NPPC for 6 h caused a large increase in cGMP concentrations, and a significant decrease in oocyte maturation (OM), an effect that was mimicked by treatment with 8-Br-cGMP. Treatment with E2 and G-1, the specific GPER agonist, also increased cGMP levels. Cyclic AMP levels were also increased by treatments with 8-Br-cGMP, E2 and G1. The estrogen upregulation of cAMP levels was blocked by co-treatment with AG1478, an inhibitor of EGFR activation. Gene expression of npr2, but not nppc, was significantly upregulated in intact oocytes by 6 h treatments with 20 nM E2 and G-1. Both cilostamide, a phosphodiesterase 3 (PDE3) inhibitor, and rolipram, a PDE4 inhibitor, significantly decreased OM of intact and defolliculated oocytes, and enhanced the inhibitory effects of E2 and G-1 on OM. These findings indicate the presence of a Nppc/Npr2/cGMP pathway maintaining meiotic arrest in zebrafish oocytes that is upregulated by estrogen activation of Gper. Collectively, the results suggest that Nppc through Npr2 cooperates with E2 through Gper in upregulation of cGMP levels to inhibit phosphodiesterase activity resulting in maintenance of oocyte meiotic arrest in zebrafish.
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