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Mitochondrial unfolding protein CLPX is required for oocyte competence during ovarian aging

GSE285263 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2025/04/01 Platform GPL30215
At a glance

RNA-seq (gene expression) · mouse · 14 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
14 samples: 4 × Clpxfl/fl GV oocyte-WT vs 4 × Clpxfl/fl; Zp3-Cre GV oocyte-CKO vs 3 × Clpxfl/f ovulated oocyte- WT vs 3 × Clpxfl/fl; Zp3-Cre ovulated oocyte-CKOGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Ovarian aging has reproductive and overall health implications with increased infertility, miscarriage rates, and adverse outcomes associated with menopause. Mitochondrial dysfunction is one of the main mechanisms of female reproductive aging. Mitochondrial protein homeostasis maintains mitochondrial function and globally dysregulated unfolded mitochondrial protein response accelerates reproductive aging.
Read the full summary ↓
However, the role of oocyte mitochondrial proteostasis in determining oocyte quality is unknown. ClpX (Caseinolytic Protease X) is a mitochondrial protein unfoldase that maintains mitochondrial protein homeostasis. In this study, we uncovered that Clpx deficiency, either through genetic ablation or natural decline with aging in mice, leads to the disrupted mitochondrial proteostasis in oocytes. Oocyte-specific knockout of Clpx impaired oocyte quality and developmental competence, thereby leading to female subfertility. Transcriptomic and micro-proteomic analyses of Clpx null oocytes revealed dysregulated mitochondrial function, protein processing and meiosis. Notably, Clpx deficiency promoted PGD2 synthesis and DP1/PKA/cAMP and DP2/AKT/mTOR signaling pathways by upregulating Ptgds. The PGD2 synthesis inhibitor AT-56 restored the developmental competence of Clpx knockout and aged oocytes. Our findings indicate the pivotal role of oocyte mitochondrial proteostasis in the regulation of oocyte quality with aging and pave the way for future investigations assessing the potential therapeutic value of these pathways to improve infertility treatment outcomes.
This dataset
Open GSE285263 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE285263_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1202134 and SRA study SRP553481. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
4 × Clpxfl/fl GV oocyte-WT vs 4 × Clpxfl/fl; Zp3-Cre GV oocyte-CKO vs 3 × Clpxfl/f ovulated oocyte- WT vs 3 × Clpxfl/fl; Zp3-Cre ovulated oocyte-CKO

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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