The potential roles of c-Jun N-terminal kinase (JNK) during the maturation and aging of oocytes produced by a marine protostome worm

Abstract

Previous investigations have indicated that c-Jun N-terminal kinase (JNK) regulates the maturation and aging of oocytes produced by deuterostome animals. In order to assess the roles of this kinase in a protostome, oocytes of the marine nemertean worm Cerebratulus were stimulated to mature and subsequently aged before being probed with phospho-specific antibodies against active forms of JNK and maturation-promoting factor (MPF). Based on blots of maturing oocytes, a 40-kD putative JNK is normally activated during germinal vesicle breakdown (GVBD), which begins at 30 min post-stimulation with seawater, whereas treating immature oocytes with JNK inhibitors downregulates both the 40-kD JNK signal and GVBD, collectively suggesting a 40-kD JNK may facilitate oocyte maturation. Along with this JNK activity, mature oocytes also exhibit high levels of MPF at 2 h post-stimulation. However, by ~6-8 h post-GVBD, mature oocytes lose the 40-kD JNK signal, and at ~20-30 h of aging, an ~48-kD phospho-JNK band arises as oocytes deactivate MPF and begin to lyse during a necroptotic-like mode of death. Accordingly, JNK inhibitors reduce the aging-related 48-kD JNK phosphorylation while maintaining MPF activity and retarding oocyte degradation. Such findings suggest that a 48-kD JNK may help deactivate MPF and trigger death. Possible mechanisms by which JNK activation either together with, or independently of, protein neosynthesis might stimulate oocyte degradation are discussed.

The Molecular Regulation in the Pathophysiology in Ovarian Aging

“…Single-cell RNA sequencing of oocytes from C57BL/6 mice of different ages revealed the following in aged mice: changes in the protein metabolism of oocytes, significant changes in the expression of genes related to protein quality control (protein modifications and the unfolded protein response), disruption of cellular components related to protein metabolism, differences in the expression of metabolismrelated proteases, and significant increases in the expression of factors associated with inflammation and the number of ribosomes in the cytosol [98]. A decline in ovarian function causes significant changes in the expression or modification of proteins such as maturation promoting factor, sirtuins (SIRT1/2/3), anti-apoptotic Bcell lymphoma 2 proteins, and caspase [108][109][110].…”