GEO series

The proprotein convertases regulate cumulus-oocyte-complex matrix integrity and cumulus cell behavior via a GDF-9 dependent mechanism

GSE331136 Mus musculus (mouse) RNA-seq (gene expression) 21 samples Submitted 2026/07/31 Platform GPL21103

At a glance

RNA-seq (gene expression) · mouse · 21 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: 21 samples: 21 samples, each with a distinct title — no replicated groupsGroups 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)

The proprotein convertases (PCSKs) are serine proteases with a wide range of biological substrates. Pcsk3, 5, and 6 expression is upregulated in the mouse follicle during ovulation, but their functions in the ovary are underexplored. Using an ex vivo ovulation assay, we observed that a PCSK inhibitor (PCI) impairs follicular rupture and reduces cumulus cell adherence to the (COC) matrix.

Read the full summary ↓

PCI treatment of COCs matured in vitro recapitulated loss of cumulus cell adherence late in the maturation period (12h) and revealed that PCI does not affect COC viability or the morphokinetics of oocyte maturation. Therefore, we hypothesized that the PCSKs have a role in maintaining structural integrity of the COC matrix. We first sought to determine which PCSKs may regulate COC matrix integrity. Using multiple approaches to assess PCSK3, 5, and 6 RNA and/or protein in the COC, we identified PCSK5A as the most likely regulator of COC matrix organization. To determine which pathways are dysregulated by PCI treatment, we conducted bulk RNA sequencing comparing control and PCI-treated COCs collected 0, 4, 8, or 12h after onset of in vitro maturation. 8h PCI-treated COCs clustered with 12h control COCs, indicating that PCI accelerates the normal temporal expression profile of COCs. Pathway analysis revealed that PCI treatment upregulated pathways related to metabolism and cell motility, and downregulated pathways corresponding to ECM organization, cell adhesion, and TGF-beta signaling. We then conducted proteomics of CTL vs. PCI-treated COCs at 10h to determine potential PCSK substrates that are affected by PCI treatment. Proteomics detected 79 proteins altered by PCI treatment, with functions related to ECM remodeling, cell adhesion/migration, cell signaling pathways, and metabolism. Notably, the oocyte proteome was stable with PCI treatment, consistent with earlier findings that the effect of PCI appears to be specific to cumulus cells. To validate PCI-induced ECM changes, we evaluated the PCI-treated COC matrix with H&E and a hyaluronic acid binding protein assay, which confirmed disruption of COC matrix integrity with PCSK inhibition. We then validated the effect of PCI on cumulus cell migration first with scanning electron microscopy, which revealed increased plasma membrane blebbing on the surface of PCI-treated cumulus cells. Live tracking of COC expansion showed that compared to control cumulus cells, PCI-treated cumulus cells have an increased mean square displacement and dysregulated anomalous diffusion, consistent with changes to cumulus cell migration. Based on the dysregulation of ECM organization and TGF-beta signaling pathways observed we PCI-treatment, we identified GDF9 as a substrate of interest, as it is a TGF-beta ligand with known PCSK consensus sequences and roles in COC expansion. Supplementation of recombinant GDF9 fully rescued COC matrix integrity, suggesting that GDF9 likely acts downstream of the PCSKs to regulate matrix organization. In conclusion, this study utilized a multi-omics approach to identify novel roles and molecular targets of the PCSKs in the COC during ovulation, with implications on development of fertility therapeutics and non-hormonal contraceptives.

This dataset

Open GSE331136 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 GSE331136_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 PRJNA1466937 and SRA study SRP700974. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

21 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 21 sample titles: 21 distinct titles with little repetition. 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

GSM9739565 COCs, biol rep 1, 0h
GSM9739566 COCs, CTL, biol rep 1, 4h
GSM9739567 COCs, PCI, biol rep 1, 4h
GSM9739568 COCs, CTL, biol rep 1, 8h
GSM9739569 COCs, PCI, biol rep 1, 8h
GSM9739570 COCs, control, biol rep 1, 12h
GSM9739571 COCs, PCI, biol rep 1, 12h
GSM9739572 COCs, biol rep 2, 0h
GSM9739573 COCs, CTL, biol rep 2, 4h
GSM9739574 COCs, PCI, biol rep 2, 4h
GSM9739575 COCs, CTL, biol rep 2, 8h
GSM9739576 COCs, PCI, biol rep 2, 8h
GSM9739577 COCs, CTL, biol rep 2, 12h
GSM9739578 COCs, PCI, biol rep 2, 12h
GSM9739579 COCs, biol rep 3, 0h
GSM9739580 COCs, CTL, biol rep 3, 4h
GSM9739581 COCs, PCI, biol rep 3, 4h
GSM9739582 COCs, CTL, biol rep 3, 8h
GSM9739583 COCs, PCI, biol rep 3, 8h
GSM9739584 COCs, CTL, biol rep 3, 12h
GSM9739585 COCs, PCI, biol rep 3, 12h

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