Inhibition of c-Jun N-terminal kinase (JNK) suppresses porcine oocyte ageing in vitro

Abstract

ABSTRACT:Oocyte ageing is a complex of processes that occur when matured in vitro oocytes are, after reaching the metaphase II stage, exposed to further in vitro culture. Aged oocytes remaining at the metaphase II stage undergo spontaneous parthenogenetic activation, or cellular death, through apoptosis (fragmentation) or lysis. The key factor in apoptotic pathway regulation is c-Jun-N-terminal kinase (JNK), stress kinase from the mitogene-activated protein kinase (MAPK) family. To investigate the effect of JNK inhibition on porcine oocytes ageing, cleavage rate, and embryonic development after parthenogenetic activation, DNA fragmentation, and pro-apoptotic factor Bax expression, we cultured in vitro matured oocytes for another 1-4 days in the presence of a JNK inhibitor. The inhibition of JNK significantly protected the oocytes from fragmentation (0% of fragmented oocytes under JNK inhibition vs. 13.4% of fragmented oocytes in the control group, 2 nd day of ageing) and increased the percentage of parthenogenetically activated oocytes (82 vs 57.7%, 2 nd day of ageing). The embryonic development of oocytes parthenogenetically activated after 24 h of ageing was influenced by JNK inhibition as well. The percentage of oocytes at the morula stage, after seven days of cultivation, was significantly increased when oocytes aged in the presence of a JNK inhibitor (42.5%) by comparison to the percentage of oocytes exposed to ageing in an inhibitor-free medium (23.3%). DNA fragmentation was significantly suppressed by JNK inhibition from the 1 st day of ageing, but the expression of pro-apoptotic factor Bax in the oocytes was not influenced. On the basis of our experiments, we can conclude that JNK inhibition suppresses apoptosis and DNA fragmentation of aged oocytes and improves their embryonic development following the parthenogenetic activation. However, to completely eliminate all ageing related processes is insufficient.

Bisphenol S instead of bisphenol A: a story of reproductive disruption by regretable substitution - a review

“…Exposure to BPS disrupts cellular signalling in the apoptotic and survival pathways (Salvesen and Walsh 2014). Evidently, it is possible to expect the interference of BPS in signal pro-apoptotic pathways and signal cascades described also in gametes, leading to an altered cell cycle and cell death Sedmikova et al 2013). Further studies focused on the mechanism of BPS action are needed for a full understanding its negative effect on reproduction on the gamete level and cell cycle regulation.…”

Mechanisms of lipid metabolism promoted by berberine via peroxisome proliferator‐activated receptor gamma during in vitro maturation of porcine oocytes

“…Hiraga et al (2013) showed that increased lipid content in porcine oocytes could reduce the development rate of IVF blastocysts, which is consistent with our results. In addition, JNK inhibitor could inhibit apoptosis and DNA division of aging oocytes and increase the development rate of embryos after parthenogenetic activation (Sedmikova et al, 2013). The addition of 20‐μM JNK inhibitor (SP600125) in mouse embryonic culture medium could significantly reduce blastocyst apoptosis and increase blastocyst development rate (Li, 2006).…”

Anti-apoptotic properties of carbon monoxide in porcine oocyte duringin vitroaging

“…Beside the modulation of ROS levels, CO can modulate activity of c-jun terminal kinase (JNK), a member of the MAPK family. In somatic cells, CO decreases the activity of JNK ( Morse et al, 2003 ) while in aging of porcine oocytes, it leads to the decrease of its activity and suppression of apoptosis ( Sedmíková et al, 2013 ). Additionally, CO may suppress apoptosis through the modulation of the level of Ca 2+ .…”