Maternal age-related differential global expression profiles observed in human oocytes

Abstract

The age-related decline in female fertility has been attributed to a variety of causes including progressive oocyte depletion, meiotic irregularities and mitochondrial dysfunction. However, additional factors could potentially be involved. To explore this possibility, comprehensive analysis of gene expression in human oocytes, discarded following IVF procedures and segregated by age, was undertaken using microarray methods. These findings indicate that the expression of oocyte genes, in a variety of major functional categories including cell cycle regulation, cytoskeletal structure, energy pathways, transcription control, and stress responses, are influenced by maternal age. These results are corroborated by a complementary extensive study using mouse oocytes.

Reduced ability to recover from spindle disruption and loss of kinetochore spindle assembly checkpoint proteins in oocytes from aged mice

“…This may reflect a general decline in whole-oocyte levels of these proteins, something that, with respect to Mad2, is supported by lowered transcript levels and is observed in both mice and humans. 24,25,27 Considering levels of staining for ACA were also lower, we suggest their loss may mark a general decline in proteins associated with the centromere, kinetochore, and possibly all heterochromatin-proteins that likely include cohesins, a suggestion supported by the measured increases in iKT distances with age. It is interesting to note there might be some association between reduced SAC proteins and cohesion loss with maternal age, which is supported by a recent report showing that cohesin deterioration may compromise SAC function by impairing sister kinetochore biorientation and its SAC signal production in mouse oocytes.…”

“…1,[15][16][17][18] However, the SAC is not as stringent in mouse oocytes as it is in somatic cells, [19][20][21][22][23] and in human and mouse oocytes, aging is associated with a reduction in levels of SAC components such as Mad2. [24][25][26][27] Although these data offer credence for a SAC basis to the maternal aging phenomenon, there are other studies demonstrating the SAC is active in aged oocytes. 7,28 First, oocytes of aged and young mice seem to share the same ability to arrest in response to nocodazole-induced spindle damage.…”

The association between the oocyte pool and aneuploidy: a comparative study of the reproductive potential of young and aged mice

“…At least in mice, the loss of chromosomeassociated cohesions in aging oocytes is associated with aneuploidy [19,20]. It is reported that the expression of oocyte genes that are related to cell cycle regulation, cytoskeleton structure, metabolic pathways, transcription control, and stress responses, were influenced by maternal age [43]. In this study, no difference in the relative expression levels of the SMC3, SMC1β and STAG3 mRNAs between the groups was observed, and no REC8 mRNA expression was found (Supplementary Data Figure 1), most likely because little or no Cohesin turnover occurs for over 2 weeks during oocyte growth [44].…”

Etiology of Down Syndrome: Risk of Advanced Maternal Age and Altered Meiotic Recombination for Chromosome 21 Nondisjunction

“…The 'biological aging' can also be interpreted in term of senescence associated degradation of ovarian protein components that are implicated in chromosome separation system in oocyte (Sherman 2005). Interestingly, level of hundred of transcripts, including cell cycle genes have been reported to decrease with increased maternal age in mice and women (Hamatani et al, 2004;Steuerwald et al, 2007).…”