Lapatinib inhibits meiotic maturation of porcine oocyte cumulus complexes cultured in vitro in gonadotropin supplemented medium
Lapatinib, which is used in breast cancer treatment, inhibits resumption of meiosis in porcine oocyte-cumulus complexes.
Eva Nagyova, Ph.D., Lucie Nemcova, Ph.D., Alzbeta Mlynarcikova, Ph.D., Sona Scsukova, Ph.D., Jaroslav Kalous, Ph.D.
Volume 99, Issue 6, Pages 1739-1748, May 2013
To determine whether inhibition of epidermal growth factor receptor (EGFR) tyrosine kinase with lapatinib affects oocyte maturation, expression of the cumulus expansion-associated genes (tumor necrosis factor alpha-induced protein 6, TNFAIP6; prostaglandin-endoperoxide synthase 2, PTGS2), and synthesis of hyaluronan (HA) and progesterone by porcine oocyte-cumulus complexes (OCC).
Our work focuses on lapatinib, an orally active small molecule that selectively inhibits the tyrosine kinase domain of both EGFR and HER2, and downstream signaling.
A reproductive biology laboratory.
Porcine OCC were cultured in vitro in a medium with FSH/LH in the presence/absence of lapatinib.
Main Outcome Measure(s):
Methods performed: real-time reverse transcriptase-polymerase chain reaction, immunofluorescence, radioimmunoassay.
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-labeling pattern were detected in lapatinib-pretreated OCC. The expression of TNFAIP6 and PTGS2 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 following OCC stimulation with FSH/LH, was significantly decreased by lapatinib (10μM).
Lapatinib inhibits oocyte maturation and reduces expression of cumulus expansion-associated transcripts, and synthesis of HA and progesterone in OCC cultured in vitro in FSH/LH-supplemented medium.