Maternal age effect on mouse oocytes: new biological insight from proteomic analysis

Abstract

The long-standing view of 'immortal germline vs mortal soma' poses a fundamental question in biology concerning how oocytes age in molecular terms. A mainstream hypothesis is that maternal ageing of oocytes has its roots in gene transcription. Investigating the proteins resulting from mRNA translation would reveal how far the levels of functionally available proteins correlate with mRNAs and would offer novel insights into the changes oocytes undergo during maternal ageing. Gene ontology (GO) semantic analysis revealed a high similarity of the detected proteome (2324 proteins) to the transcriptome (22 334 mRNAs), although not all proteins had a cognate mRNA. Concerning their dynamics, fourfold changes of abundance were more frequent in the proteome (3%) than the transcriptome (0.05%), with no correlation. Whereas proteins associated with the nucleus (e.g. structural maintenance of chromosomes and spindle-assembly checkpoints) were largely represented among those that change in oocytes during maternal ageing; proteins associated with oxidative stress/damage (e.g. superoxide dismutase) were infrequent. These quantitative alterations are either impoverishing or enriching. Using GO analysis, these alterations do not relate in any simple way to the classic signature of ageing known from somatic tissues. Given the lack of correlation, we conclude that proteome analysis of mouse oocytes may not be surrogated with transcriptome analysis. Furthermore, we conclude that the classic features of ageing may not be transposed from somatic tissues to oocytes in a one-to-one fashion. Overall, there is more to the maternal ageing of oocytes than mere cellular deterioration exemplified by the notorious increase of meiotic aneuploidy.

Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain

“…However, under some conditions (i.e., aging or disease) the genome defensive system becomes vulnerable due to loss of function, reduced expression level or misregulation of proteins important for genome maintenance. For example, decreased transcripts of SAC components Bub1 and Mad2 and reduced levels of cohesin proteins were observed during normative aging in oocytes (Schwarzer et al, 2014; Steuerwald et al, 2001; Tsutsumi et al, 2014), which might be related to the increased aneuploidy with age in these cells. Gene expression analysis of murine tissues previously shown to undergo age-related aneuploidization (Baker et al, 2013; Faggioli et al, 2012) revealed age-associated down-regulation of proteins important for chromosome segregation, such as components of the SAC and centromere proteins (Zahn et al, 2007)(Fig.…”

Can cytoplasmic donation rescue aged oocytes?

“…In addition, mouse oocyte aging changes the mRNA and protein expression. Dysfunctions of the aged ovary may be responsible for the changes . For maintenance of DNA methylation, DNMT1 is expressed in mouse oocytes, but its defect disturbs the expression of imprinted genes during early embryonic development .…”

Insights into Mechanisms Causing the Maternal Age-Induced Decrease in Oocyte Quality

“…One mechanism involved in the etiology of increased aneuploidy with advanced maternal age is decreased levels of the cohesin proteins [ 31 ]. Therefore, investigators created genetic mouse models to mimic this decrease and answer specifi c questions about the roles of cohesin proteins during meiosis.…”