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Physiologic variation in sperm miRNAs tunes embryonic gene regulatory programs and developmental outcomes

GSE322558 Mus musculus (mouse) Non-coding RNA profiling 622 samples Submitted 2026/04/13 Platform GPL32159
At a glance

Non-coding RNA profiling · mouse · 622 samples

What it is
Non-coding RNA profilingLevels of RNAs that do not code for proteins, such as miRNA or lncRNA.
Organism
Mus musculus (mouse)
Samples
622 samples: 18 conditions, mostly with about 24 replicates eachGroups 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.
Paper
Physiologic variation in sperm miRNAs tune embryonic gene regulatory programs and developmental outcomesbioRxiv : the preprint server for biology · 2026
Summary (written by the submitters)
Small RNAs delivered by sperm can transmit environmentally regulated, epigenetically inherited phenotypes to offspring, yet the mechanisms by which modest changes in sperm microRNA (miRNA) abundance overcome dilution within the much larger egg to influence embryonic development remain unresolved. Here, we show that physiologically relevant variation in individual sperm miRNAs is sufficient to quantitatively program embryonic gene expression and developmental outcomes.
Read the full summary ↓
Using parthenogenetic and fertilized embryos, we show that as few as 200 molecules of miR-200c-3p or miR-465c-3p induces reproducible, dose-dependent gene expression responses that are restricted to defined developmental windows. Parthenogenetic embryos faithfully recapitulate early miRNA-driven gene expression changes observed in fertilized embryos, validating their use for isolating early regulatory mechanisms. We further developed Ago-REMORA, an RNA adenosine base editor fused to Argonaute 2 to map miRNA–mRNA interactions in embryos, revealing that early mRNA repression reflects direct miRNA targeting, while transcriptional changes at later stages arise indirectly from propagation of early regulatory events. Furthermore, we show that modest elevation of miR-200c-3p during early development is sufficient to induce transcriptional alterations through early development and produce craniofacial phenotypes in late-stage embryos, recapitulating features of fetal alcohol syndrome associated with paternal alcohol consumption. Together, these findings establish a generalizable framework by which small perturbations in sperm miRNA content quantitatively modulate early gene regulatory programs, triggering cascades that persist throughout development and influence offspring phenotype.
Published in
Physiologic variation in sperm miRNAs tune embryonic gene regulatory programs and developmental outcomes
Lee GS, Garifallou J, Higgins SL et al. · bioRxiv : the preprint server for biology 2026 · PMID 41867768 · doi:10.64898/2026.03.04.709527
This dataset
Open GSE322558 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 GSE322558_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 ↗

Also filed as BioProject PRJNA1430421 and SRA study SRP680228. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41867768) ↗
Study design
18 conditions, mostly with about 24 replicates each
parth200_2cell_control ×28 parth200_2cell_low_miR200 ×26 parth200_4cell_control ×24 parth200_4cell_high_miR200 ×24 parth200_morula_low_miR200 ×24 parth465_4cell_low_miR465 ×24 parth200_2cell_mid_miR200 ×23 parth200_4cell_low_miR200 ×23 +10 more

Supports a between-group comparison across 400 samples.

How we read this: 18 replicated groups read from the first 400 of 622 sample titles; they account for 400 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

+ 582 more — browse all 622 samples with per-sample file links →

Datasets on a similar topic

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