Role of autophagy in modulating post-maturation aging of mouse oocytes.

ABSTRACT: Mechanisms for post-maturation oocyte aging (PMOA) are not fully understood, and whether autophagy plays any role in PMOA is unknown. To explore the role of autophagy in PMOA, expression of autophagosomes and effects of the autophagy (macro-autophagy) activity on PMOA were observed in mouse oocytes. Oocyte activation rates and active caspase-3 levels increased continuously from 0 to 18?h of in vitro aging. While levels of microtubule-associated protein light chain 3 (LC3)-II increased up to 12?h and decreased thereafter, contents of p62 decreased from 0 to 12?h and then elevated to basal level by 18?h. However, the LC3-II/I ratio remained unchanged following aging in different media or for different times. During in vitro aging up to 12?h, upregulating autophagy with rapamycin or lithium chloride decreased activation susceptibility, cytoplasmic calcium, p62 contents, oxidative stress, caspase-3 activation and cytoplasmic fragmentation while increasing developmental competence, LC3-II contents, LC3-II/I ratio, mitochondrial membrane potential, spindle/chromosome integrity and normal cortical granule distribution. Downregulating autophagy with 3-methyladenine (3-MA) produced opposite effects on all these parameters except cytoplasmic fragmentation. After 12?h of aging culture, however, regulating autophagy with either rapamycin/lithium chloride or 3-MA had no impact on oocyte activation susceptibility. It is concluded that autophagy plays an important role in regulating PMOA. Thus, during the early stage of PMOA, autophagy increases as an adaptive response to prevent further apoptosis, but by the late stage of PMOA, the activation of more caspases blocks the autophagic process leading to severer apoptosis.

SUBMITTER: Lin FH 

PROVIDER: S-EPMC5833823 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature