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.

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Authors

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

Abstract

Objective:

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).

Design:

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.

Setting:

A reproductive biology laboratory.

Patients:

Not applicable.

Intervention(s):

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.

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-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).

Conlusion(s):

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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(13)00002-2/fulltext


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