GEO series

Persistent dopamine-dependent remodeling of the neural transcriptome in response to pregnancy and postpartum [bulk RNA-seq]

GSE289991 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing 294 samples Submitted 2026/04/13 Platform GPL34328Platform GPL34290Platform GPL34284Platform GPL24247

Summary

Pregnancy and postpartum experiences represent transformative physiological states that impose lasting demands on the maternal body and brain, resulting in lifelong neural adaptations. However, the precise molecular mechanisms driving these persistent alterations remain poorly understood. Here, we used brain-wide transcriptomic profiling to define the molecular landscape of parity-induced neural plasticity, identifying the dorsal hippocampus (dHpc) as a key site of transcriptional remodeling. Combining single-cell RNA sequencing with a maternal separation paradigm, we additionally demonstrated that chronic postpartum stress significantly disrupts dHpc adaptations by altering dopamine dynamics, leading to dysregulated transcription, altered cellular plasticity, and impaired behavior. We further established the sufficiency of dopamine modulation in the regulation of these parity-induced adaptations via chemogenetic suppression of dopamine release into dHpc, which recapitulated key transcriptional and behavioral features of parity in virgin females. In sum, our findings establish dopamine as a central regulator of parity-induced neuroadaptations, revealing a fundamental transcriptional mechanism by which female reproductive experiences remodel the maternal brain to sustain long-term behavioral adaptations.

Published in

Dopamine drives persistent remodelling of the maternal brain

O'Chan JC, Di Salvo G, Cunningham AM et al. · Nature 2026 · PMID 42162419 · doi:10.1038/s41586-026-10509-4

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Direct links to NCBI, no account and no request form: the whole study as GSE289991_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 294 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1225705 and SRA study SRP565042. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42162419) ↗

Study design

14 × dHipp vs 13 × mPFC vs 13 × vHipp

Supports a between-group comparison across 40 samples.

3 replicated groups read from the first 40 of 294 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.

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