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9-cis retinoic acid inhibits cumulus cell apoptosis during the maturation of bovine cumulus-oocyte-complexes.
MedLine Citation:
PMID:  22205673     Owner:  NLM     Status:  Publisher    
Cumulus cell (CC) apoptosis is inversely correlated with embryonic development in vitro. Therefore, inhibition of CC apoptosis is important for proper embryonic development and quality. Retinoic acids (all-transRA and 9-cisRA) are the natural components of retinoids and the 9-cisRA is the physiologically active metabolite of retinoic acid in vitro. During in vitro maturation, 9-cisRA enhances oocyte competence through multiple mechanisms affecting the oocyte and the preimplantation embryo; however, the effect of 9-cisRA on CC apoptosis has yet to be elucidated. The aim of the present study was to evaluate the effect of 9-cisRA on CC apoptosis and to identify the molecular mechanism underlying that effect. Bovine slaughterhouse cumulus-oocyte-complexes (COC) were matured in vitro in the absence or presence of 5 nM 9-cisRA. Cumulus cells were collected from immature and matured COC for the detection of apoptosis and gene expression analysis. Results showed that 9-cisRA reduced the number of apoptotic CC by about 2.7-fold (P < 0.023) compared to the control. However, apoptosis is rare in CC of immature COC (0.01% ± 0.001). Transcripts involved in the caspase cascade were down-regulated upon exposure to 9-cisRA, including tumor necrosis factor alpha (TNF-α, 11.1-fold, P < 0.001), tumor necrosis factor alpha receptor 1 (TNFR1, 2.3-fold, P < 0.01), caspase 9 (CASP9, 2.0-fold, P < 0.031), caspase 8 (CASP8, 2.2-fold, P < 0.012), and caspase 3 (CASP3, 2.1-fold, P < 0.006), while anti-apoptotic B-cell lymphoma 2 (BCL2) transcript was increased (3.1-fold, P < 0.004) compared to the control. In addition, 9-cisRA inhibited mitogen activated protein kinase mRNA expression in CC, including extracellular signal-regulated kinase 1/2 (ERK1, 2.7-fold, P < 0.02; ERK2, 2.7-fold, P < 0.03), and c-Jun N-terminal kinase (JNK, 1.6-fold, P < 0.044), as well as the activator protein-1 (AP1) family members c-jun (1.6-fold, P < 0.041) and c-fos (2.0-fold, P < 0.06). The transcript abundances of TNF-α, TNFR1, CASP9, CASP8, CASP3, ERK1, ERK1, JNK, and BCL2 were increased while c-fos and c-jun mRNA expression was decreased in the matured CC. In conclusion, the present study suggests that 9-cisRA inhibits CC apoptosis during in vitro maturation of bovine COC.
G K Deb; S R Dey; J I Bang; J G Lee; I K Kong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-28
Journal Detail:
Title:  Journal of animal science     Volume:  -     ISSN:  1525-3163     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8003002     Medline TA:  J Anim Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Division of Applied Life Science (BK21 Program), Graduate School of Gyeongsang National University.
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