The Roles of c-Jun N-terminal Kinase (JNK) and p38 Mitogen-activated Protein Kinase (p38 MAPK) in Aged Pig Oocytes

Abstract

Abstract. After reaching metaphase II, in vitro matured oocytes undergo the complex processes referred to as oocyte aging. Under our culture conditions, some aged oocytes remained at the stage of metaphase II, some underwent spontaneous parthenogenetic activation and others underwent cellular death, either through apoptosis (fragmentation) or lysis. We investigated the effect of c-Jun N-terminal kinases (JNK) and p38 Mitogen-activated protein kinase (p38 MAPK) inhibition on pig oocyte aging and the activity of JNK and p38 MAPK during the aging period. Inhibition of JNK protected the oocytes from fragmentation (0% fragmented oocytes under JNK inhibition vs. 26% fragmented oocytes in the control group). Inhibition of p38 MAPK had no effect on fragmentation. Inhibition of JNK also had an influence on spontaneous parthenogenetic activation of aged oocytes. The ratio of activated JNK to total JNK decreased during aging of oocytes. However, exit from MII had no effect on it. The ratio of activated p38 MAPK to total p38 MAPK did not change significantly. The phosphorylated form of JNK is present in fragmented and activated oocytes, while lysed oocytes lack the active form of JNK. Based on our data, we can conclude that JNK plays an active role in fragmentation of pig oocytes and that p38 MAPK is not involved in this process.

De novo synthesis of protein phosphatase 1A, magnesium dependent, alpha isoform (PPM1A) during oocyte maturation

“…The cascade of ERK-MAPK, a member of the MAPK family, was extensively studied and was shown to be essential for the development of healthy mature rodent oocytes [20]. The less studied p38-MAPK cascade was suggested to be involved in maturation of porcine [21] and Xenopus [22] oocytes. In view of the fact that PPM1A is a known phosphatase of p38-MAPK [23], and of our findings showing that PPM1A is up-regulated in mouse oocytes during the transition from GV to MII, we examined the kinase activity of p38-MAPK during maturation of mouse oocytes and found that the level of phospho-p38-MAPK (Phos-p38) was higher in GV oocytes than in MII oocytes (Fig.…”

From Nitric Oxide Toward S-Nitrosylation: Expanding Roles in Gametes and Embryos

“…Oocyte aging rapidly decreases their quality and capacity to undergo embryonic development after fertilization. Functional and morphological changes associated with oocyte aging include decreased fertilization rates, polyspermy, parthenogenetic activation, apoptosis, chromosomal abnormalities, cortical granules exocytosis, ooplasmic microtubule dynamics, zona pellucida hardening, decreases in MPF and MAPK activities, epigenetic changes, and abnormal or delayed embryo development [24,[68][69][70][71]. Pathological conditions of oocyte aging impose limits for assisted reproduction technologies in animals as well as in humans [72].…”

Molecular alterations during female reproductive aging: Can aged oocytes remind youth?

“…Although how these signaling molecules are involved in oocyte activities remains uncertain, JNK, but not p38 MAPK, was found to participate in oocyte fragmentation and parthenogenetic activation in aged oocytes (Petrova et al 2009). …”