title: Lapatinib inhibits meiotic maturation of porcine oocyte-cumulus complexes cultured in vitro in gonadotropin-supplemented medium.
abstract: OBJECTIVE
  To determine whether inhibition of epidermal growth factor (EGF) receptor tyrosine kinase with lapatinib affects oocyte maturation, expression of the cumulus expansion-associated genes such as tumor necrosis factor alpha-induced protein 6 (TNFAIP6) and prostaglandin-endoperoxide synthase 2 (PTGS2), and synthesis of hyaluronan (HA) and progesterone (P) by porcine oocyte cumulus complexes (OCC).
  
  
  METHODS
  Our work focuses on lapatinib, an orally active small molecule that selectively inhibits the tyrosine kinase domain of both EGF receptor and human EGF receptor 2, and downstream signaling.
  
  
  METHODS
  A reproductive biology laboratory.
  
  
  METHODS
  Not applicable.
  
  
  METHODS
  Porcine OCC were cultured in vitro in a medium with FSH/LH in the presence/absence of lapatinib.
  
  
  METHODS
  Methods performed: real-time reverse transcriptase-polymerase chain reaction (PCR), immunofluorescence, RIA.
  
  
  RESULTS
  In FSH/LH-stimulated and expanded cumulus oophorus extracellular matrix, HA was detected with biotinylated HA-binding proteins. However, weaker HA- and weaker cytoplasmic TNFAIP6 were detected were detected in lapatinib-pretreated OCC. The expression of the two cumulus expansion-associated gene transcripts was significantly decreased and synthesis of HA by cumulus cells was reduced. Lapatinib (10 μM) inhibited FSH/LH-induced oocyte meiotic maturation. Progesterone production increased after OCC stimulation with FSH/LH and was significantly decreased by lapatinib (10 μM).
  
  
  CONCLUSIONS
  Lapatinib inhibits oocyte maturation and reduces expression of cumulus expansion-associated transcripts, and synthesis of HA and P in OCC cultured in vitro in FSH/LH-supplemented medium.
authors: Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov, Czech Republic. nagyova@iapg.cas.cz
authors: Eva
authors: E
authors: Nagyova
authors: Lucie
authors: L
authors: Nemcova
authors: Alzbeta
authors: A
authors: Mlynarcikova
authors: Sona
authors: S
authors: Scsukova
authors: Jaroslav
authors: J
authors: Kalous
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D000077341:Lapatinib; D008540:Meiosis / Q000187:drug effects* / Q000502:physiology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects*; D011799:Quinazolines / Q000494:pharmacology*; D013552:Swine
chemical_list: D006131:Growth Inhibitors; D011799:Quinazolines; D000077341:Lapatinib; D005640:Follicle Stimulating Hormone