Comprehensive analysis of miRNA–mRNA interactions in ovaries of aged mice

Abstract

Advanced maternal age and ovarian aging are deleterious to the quantity and quality of oocytes and epigenetic modifications, which can affect the health of offspring. However, relatively little is known about the regulation of microRNA‐mediated transcription during ovarian aging. We therefore aimed to identify age‐related mRNA and microRNA changes and their interactions in the ovaries of aged mice. We performed QuantSeq 3′mRNA and small RNA sequencing to compare their expression patterns in post‐ovulation ovaries from young (12‐week‐old) and old (44‐week‐old) mice. Functional annotation and integrative analyses were performed to identify the potential functions of differentially expressed genes and identify binding sites for critical microRNAs. We found 343 differentially expressed genes and 9 microRNAs in our comparison of the two mouse groups, with fold changes >2.0 ( P < 0.01). Furthermore, we identified possible direct interactions between 24 differentially expressed mRNAs and 8 microRNAs. The differentially expressed genes are involved in fat digestion and absorption, the PI3K‐Akt signaling pathway, serotonergic synapse, and ovarian steroidogenesis, which are important for folliculogenesis and oocyte growth. During ovarian aging, changes in gene expression induce alterations in folliculogenesis, oocyte growth, and steroidogenesis, resulting in decreased oocyte quality and reproductive outcomes.

Role and Mechanism of Epigenetic Regulation in the Aging of Germ Cells: Prospects for Targeted Interventions

“…For example, miR-19b was highly enriched in the follicular fluid (FF), GCs of young cows and regulates genes associated with FoxO signaling, endocytosis, and NR3C1 in GCs [117]. Differentially expressed genes and miRNA interacted in young and senescent mice, which influenced folliculogenesis, oocyte growth and steroidogenesis [118]. It was shown that the expression of miR-23a and miR-27a was significantly higher in aged rats than in controls [119].…”

Prenatal Exposure to Delta-9-tetrahydrocannabinol (THC) Alters the Expression of miR-122-5p and Its Target Igf1r in the Adult Rat Ovary

“…MiRNAs are small, endogenous, noncoding single-stranded RNA molecules with a length of approximately 22 to 24 nucleotides, which act as posttranscriptional regulators of gene expression [ 49 , 50 ]. Mature miRNAs can regulate gene expression through different mechanisms, including mRNA cleavage and translational inactivation [ 51 ].…”