PMID- 22949725
OWN - NLM
STAT- MEDLINE
DCOM- 20130408
LR  - 20181202
IS  - 1741-7899 (Electronic)
IS  - 1470-1626 (Linking)
VI  - 144
IP  - 5
DP  - 2012 Nov
TI  - Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption 
      and cumulus cell expansion in the pig.
PG  - 535-46
LID - 10.1530/REP-12-0191 [doi]
AB  - To define signaling pathways that drive FSH- and epidermal growth factor 
      (EGF)-like peptide-induced cumulus expansion and oocyte meiotic resumption, in 
      vitro cultured pig cumulus-oocyte complexes were treated with specific protein 
      kinase inhibitors. We found that FSH-induced maturation of oocytes was blocked in 
      germinal vesicle (GV) stage by protein kinase A (PKA), MAPK14, MAPK3/1, and EGF 
      receptor (EGFR) tyrosine kinase inhibitors (H89, SB203580, U0126, and AG1478 
      respectively) whereas phosphoinositide-3-kinase/v-akt murine thymoma viral 
      oncogene homolog (PI3K/AKT) inhibitor (LY294002) blocked maturation of oocytes in 
      metaphase I (MI). Amphiregulin (AREG)-induced maturation of oocytes was 
      efficiently blocked in GV by U0126, AG1478, and low concentrations of LY294002; 
      H89, SB203580, and high concentrations of LY294002 allowed the oocytes to undergo 
      breakdown of GV and blocked maturation in MI. Both FSH- and AREG-induced cumulus 
      expansion was incompletely inhibited by H89 and completely inhibited by SB203580, 
      U0126, AG1478, and LY294002. The inhibitors partially or completely inhibited 
      expression of expansion-related genes (HAS2, PTGS2, and TNFAIP6) with two 
      exceptions: H89 inhibited only TNFAIP6 expression and LY294002 increased 
      expression of PTGS2. The results of this study are consistent with the idea that 
      PKA and MAPK14 pathways are essential for FSH-induced transactivation of the 
      EGFR, and synthesis of EGF-like peptides in cumulus cells and MAPK3/1 is involved 
      in regulation of transcriptional and posttranscriptional events in cumulus cells 
      required for meiotic resumption and cumulus expansion. PI3K/AKT signaling is 
      important for regulation of cumulus expansion, AREG-induced meiotic resumption, 
      and oocyte MI/MII transition. The present data also indicate the existence of an 
      FSH-activated and PKA-independent pathway involved in regulation of HAS2 and 
      PTGS2 expression in cumulus cells.
FAU - Prochazka, R
AU  - Prochazka R
AD  - Laboratory of Developmental Biology, , Institute of Animal Physiology and 
      Genetics, Academy of Sciences of the Czech Republic, Rumburska 89, 277 21 
      Libechov, Czech Republic. prochazka@iapg.cas.cz
FAU - Blaha, M
AU  - Blaha M
FAU - Nemcova, L
AU  - Nemcova L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120904
PL  - England
TA  - Reproduction
JT  - Reproduction (Cambridge, England)
JID - 100966036
RN  - 0 (Amphiregulin)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 14)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Cumulus Cells/*physiology
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/physiology
MH  - Cyclooxygenase 2/genetics
MH  - ErbB Receptors/physiology
MH  - Female
MH  - Follicle Stimulating Hormone/*pharmacology
MH  - Gene Expression Regulation/physiology
MH  - Glucuronosyltransferase/genetics
MH  - Glycoproteins/*pharmacology
MH  - Intercellular Signaling Peptides and Proteins/*pharmacology
MH  - Meiosis/*drug effects/physiology
MH  - Mitogen-Activated Protein Kinase 14/antagonists & inhibitors/physiology
MH  - Oocytes/drug effects/physiology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Signal Transduction/drug effects/*physiology
MH  - Sus scrofa/*physiology
EDAT- 2012/09/06 06:00
MHDA- 2013/04/09 06:00
CRDT- 2012/09/06 06:00
PHST- 2012/09/06 06:00 [entrez]
PHST- 2012/09/06 06:00 [pubmed]
PHST- 2013/04/09 06:00 [medline]
AID - REP-12-0191 [pii]
AID - 10.1530/REP-12-0191 [doi]
PST - ppublish
SO  - Reproduction. 2012 Nov;144(5):535-46. doi: 10.1530/REP-12-0191. Epub 2012 Sep 4.