Single-cell atlas of the developing mouse oviduct reveals smooth muscle heterogeneity and identifies Vps34 as a critical regulator of female fertility
4 affiliations
- 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- 2Department of Obstetrics and Gynecology, Affiliated Hospital of Medical School, Jinling Hospital, Nanjing University, Nanjing, China
- 3The Second Clinical Medical College, Nanjing Medical University, Nanjing, China
- 4Department of Prenatal Diagnosis, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing, China
Abstract
Background: The oviduct smooth muscle layer is traditionally regarded as a contractile unit. Limited understanding exists regarding the molecular heterogeneity and intercellular communication during development timeline, which is critical for female reproductive function. To address this, we performed single-cell RNA sequencing (scRNA-seq) to profile the cellular composition of mice oviducts at four developmental stages: neonatal (7 days), pre-pubertal (3 weeks), young adult (8 weeks) and middle-aged (9 months). We aim to provide a framework for further investigation of oviduct biology and associated reproductive disorders.
Results: We delineate three distinct (SMC) subtypes, with their relative proportions shifting dynamically across the developmental timeline. SMC1 represented a transient progenitor population exclusive to neonatal oviducts. SMC2 displayed a mature contractile phenotype, while SMC3 uniquely expressed hormone-responsive genes (Esr1, Pgr) and showed enrichment of autophagy-related pathways. Functional studies demonstrated that SMC-specific deletion of Vps34 disrupts oviduct coiling and muscular integrity, leading to vacuolar degeneration and a significant reduction in litter size in mice. Additionally, we map five ciliated and six secretory epithelial subtypes and suggest that FN1 signaling may serve as a potential mediator of crosstalk between epithelial and SMCs during development, with the FN1-SDC4 axis emerging as the dominant interaction in mature oviducts. Thus, while the contractile and hormone-responsive functions of the oviductal muscle layer have long been recognized, our work provides its underlying cellular complexity during development.
Conclusion: Our study constructs a developmental atlas of murine oviduct SMCs, revealing that the myosalpinx is composed of functionally distinct SMC subtypes with dynamic developmental trajectories. The identification of Vps34 as a critical guardian of myosalpinx integrity offers a new cellular framework for understanding human tubal pathologies. These findings highlight the importance of SMC subtype homeostasis and autophagy-mediated maintenance of myosalpinx structure, providing a basis for future mechanistic studies on oviduct function and dysfunction.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12915-026-02706-4.
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BibTeX
@article{he2026singlecell,
title = {{Single-cell atlas of the developing mouse oviduct reveals smooth muscle heterogeneity and identifies Vps34 as a critical regulator of female fertility}},
author = {Yanhua He and Yong Zhang and Yunxia Chen and Lefan Ju and Wen Fang and Qian Huang and Xiaoyan Ying and Wenwen Liu and Xiaowei Dou},
journal = {BMC Biology},
year = {2026},
month = aug,
doi = {10.1186/s12915-026-02706-4},
url = {https://doi.org/10.1186/s12915-026-02706-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell atlas of the developing mouse oviduct reveals smooth muscle heterogeneity and identifies Vps34 as a critical regulator of female fertility
AU - Yanhua He
AU - Yong Zhang
AU - Yunxia Chen
AU - Lefan Ju
AU - Wen Fang
AU - Qian Huang
AU - Xiaoyan Ying
AU - Wenwen Liu
AU - Xiaowei Dou
PY - 2026
DA - 2026/08/07
JO - BMC Biology
DO - 10.1186/s12915-026-02706-4
UR - https://doi.org/10.1186/s12915-026-02706-4
AB - Background: The oviduct smooth muscle layer is traditionally regarded as a contractile unit. Limited understanding exists regarding the molecular heterogeneity and intercellular communication during development timeline, which is critical for female reproductive function. To address this, we performed single-cell RNA sequencing (scRNA-seq) to profile the cellular composition of mice oviducts at four developmental stages: neonatal (7 days), pre-pubertal (3 weeks), young adult (8 weeks) and middle-aged (9 months). We aim to provide a framework for further investigation of oviduct biology and associated reproductive disorders. Results: We delineate three distinct (SMC) subtypes, with their relative proportions shifting dynamically across the developmental timeline. SMC1 represented a transient progenitor population exclusive to neonatal oviducts. SMC2 displayed a mature contractile phenotype, while SMC3 uniquely expressed hormone-responsive genes (Esr1, Pgr) and showed enrichment of autophagy-related pathways. Functional studies demonstrated that SMC-specific deletion of Vps34 disrupts oviduct coiling and muscular integrity, leading to vacuolar degeneration and a significant reduction in litter size in mice. Additionally, we map five ciliated and six secretory epithelial subtypes and suggest that FN1 signaling may serve as a potential mediator of crosstalk between epithelial and SMCs during development, with the FN1-SDC4 axis emerging as the dominant interaction in mature oviducts. Thus, while the contractile and hormone-responsive functions of the oviductal muscle layer have long been recognized, our work provides its underlying cellular complexity during development. Conclusion: Our study constructs a developmental atlas of murine oviduct SMCs, revealing that the myosalpinx is composed of functionally distinct SMC subtypes with dynamic developmental trajectories. The identification of Vps34 as a critical guardian of myosalpinx integrity offers a new cellular framework for understanding human tubal pathologies. These findings highlight the importance of SMC subtype homeostasis and autophagy-mediated maintenance of myosalpinx structure, providing a basis for future mechanistic studies on oviduct function and dysfunction. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12915-026-02706-4.
SN - 1741-7007
ER -