Abstract
The Ames dwarf (df/df) mice have extended longevity and can preserve the ovarian reserve longer than Normal (N) mice. Based on this, the aim of our study was to evaluate the ovarian microRNA (miRNA) profile in young and aged df/df and N mice. Ovarian tissue was collected at 5–6 months and at 21–22 months of age for miRNA sequencing. We detected a total of 404 miRNAs in the ovarian samples, from which the abundance of 22 and 33 miRNAs changed with age in N and df/df mice, respectively. Of these, only three miRNAs were commonly regulated with age between N and df/df mice, indicating a very divergent miRNA profile between genotypes. We also detected that 46 miRNAs were regulated between N and df/df mice, of which 23 were regulated exclusively in young mice, 12 exclusively in old mice and 12 commonly regulated at young and old ages. Many genes likely to be targeted by these miRNAs are involved in the FoxO, mTOR, PI3k/Akt and insulin signaling pathways. These results suggest that the aging process has a differential impact on the ovarian miRNA profile in df/df mice, and suggest that these miRNAs can be central players in the maintenance of a younger ovarian phenotype.
Highlights
Regulation of gene expression plays a key role in follicle development and aging within the ovary [1]
We previously reported that Forkhead Box O3a (Foxo3a) phosphorylation, one of the main pathways implicated in irreversible primordial follicle activation [17, 18], is reduced in oocytes enclosed in primordial follicles from df/df mice, preventing primordial follicle activation [19, 20]
It was previously demonstrated that the size of the primordial follicle reserve decreases by approximately 90% from the ages of 0.5 to 1.5 years in N female mice [12], and we demonstrated before that the ovarian reserve of primordial follicles in df/df mice is three times larger than in N mice [19, 20]
Summary
Regulation of gene expression plays a key role in follicle development and aging within the ovary [1]. Some key cellular processes, including mRNA transcription and stability, are regulated by small non-coding RNAs (sncRNAs), which includes short sequences of about 20 nucleotides known as microRNAs (miRNAs) [2]. When miRNAs are exported to the cytoplasm, they modulate gene expression post-transcriptionally by interacting with the Argonaute proteins, forming an RNA Induced Silencing Complex (RISC) that binds to the 3’ untranslated region (UTR) and cleaves target mRNAs [3]. MiRNAs can be secreted to the extracellular space [4] and have a role in intercellular communication in a hormone-like pattern between different cell types [5]. MiRNAs play an essential role in ovarian. PLOS ONE | DOI:10.1371/journal.pone.0169213 January 3, 2017
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