Abstract

Aging is the main cause of decline in oocyte quality, which can further trigger the failure of assisted reproductive technology (ART). Exploring age-related genes in oocytes is an important way to investigate the molecular mechanisms involved in oocyte aging. To provide novel insight into this field, we performed a pooled analysis of publicly available datasets, using the overlapping results of two statistical methods on two Gene Expression Omnibus (GEO) datasets. The methods utilized in the current study mainly include Spearman rank correlation, the Wilcoxon signed-rank test, t-tests, Venn diagrams, Gene Ontology (GO), Protein–Protein Interaction (PPI), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and receiver operating characteristic (ROC) curve analysis. We identified hundreds of age-related genes across different gene expression datasets of in vitro maturation-metaphase II (IVM-MII) oocytes. Age-related genes in IVM-MII oocytes were involved in the biological processes of cellular metabolism, DNA replication, and histone modifications. Among these age-related genes, FAM111A expression presented a robust correlation with age, seen in the results of different statistical methods and different datasets. FAM111A is associated with the processes of chromosome segregation and cell cycle regulation. Thus, this enzyme is potentially an interesting novel marker for the aging of oocytes, and warrants further mechanistic study.

Highlights

  • Introduction iationsFemale fertility decreases progressively with age

  • A summary of the gene expression profiles included in the current analysis is shown in Figure 1A, and Figure 1B presents an overview of the analysis procedures of the study

  • Analysis of in vitro maturation-metaphase II (IVM-MII) oocytes from Group II (Supplementary Table S7), meiotic chromosome segregation, the regulation of the cell cycle, the positive regulation of the WNT signaling pathway, actin filament organization, and microtubule-associated complex, were terms significantly regulated by FAM111 Trypsin-like Peptidase A (FAM111A) (Table 1)

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Summary

Introduction

The decrease in fertility is reflected in the lower quantity and quality of oocytes. Age-related decline in oocyte quality is an important non-male cause of assisted reproductive technology (ART). Failures, and there is no successful treatment for the age-related decline in oocyte quality [2]. Increased aneuploidy is an important cause of the decline in oocyte quality [3]. Oocyte quality decline has been associated with nuclear and mitochondrial DNA damage [4,5], meiotic spindle abnormalities, chromosomal misalignment, mitochondrial dysfunction [6], telomere shortening [7], and abnormal structure of the zona pellucida [8,9]

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