A single-nucleus multiomic study of preoptic area cells in prepubertal control vs prenatally androgenized female mice.

Overview

1. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA
2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
3. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA
4. Department of Reproductive Sciences Program, University of Michigan, Ann Arbor, MI 48109, USA

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder with developmental origins. While the etiology is unclear, current postulates include epigenetic programming. Cell-type-specific epigenetic changes by which prenatal androgen excess programs the neuroendocrine axis have not been defined. Using single-nucleus (sn) multiome sequencing (single-nucleus ribonucleic acid sequencing [snRNAseq] + single-nucleus assay for transposase-accessible chromatin using sequencing [snATACseq]) of the mouse preoptic area, we profiled transcriptional and chromatin accessibility landscapes across 31 cell populations on postnatal day 18 to 22 in a prenatal androgenization (PNA) mouse model that produces neuroendocrine phenotypes that resemble hyperandrogenemic PCOS. Marker gene analysis identified 17 neuronal and 14 non-neuronal populations. We refined the gonadotropin-releasing hormone (GnRH) neuron cluster to 41 neurons by manual curation. Cross-dataset comparisons were used to characterize the molecular transcriptional identity of these clusters. Gene set enrichment analysis of mRNA expression data revealed enrichment of protein synthesis and oxidative phosphorylation pathways and suppression of TNF/NF-κB signaling and steroid responsiveness across several clusters in PNA animals. Pseudobulk differential chromatin accessibility testing across ∼30 600 peaks identified 15 false discovery rate-significant differentially accessible regions, including 2 loci in GnRH neurons at genomic regions of unknown function, suggesting prenatal androgen exposure changes chromatin accessibility in this and other cell types. Chromosome accessibility at most sex steroid receptor genes was surprisingly present in GnRH neurons. Reduced Pgk1 promoter accessibility in multiple glial populations suggests PNA alters epigenetic regulation of glial energy metabolism. These findings support a model of developmental programming in which prenatal androgen exposure produces cell-type-specific changes that include, but are not limited to, epigenetic remodeling to generate the PNA phenotype.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE318722 — at NCBI GEO; found in the references

Data availability

Original data generated and analyzed during this study are included in this published article or in the data repositories listed in references (54, 65).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 15 MeSH terms, 2 funders, 112 references.

Cite

This paper

Burger, L. L., Chikodikar, R. M., & Moenter, S. M. (2026). A single-nucleus multiomic study of preoptic area cells in prepubertal control vs prenatally androgenized female mice. Endocrinology, 167(9), bqag087. https://doi.org/10.1210/endocr/bqag087

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