Integrated single-cell and bulk transcriptomic analyses reveal UTF1-associated spermatogenic dysfunction and identify ACTRT2 and AKAP4 as biomarkers in non-obstructive azoospermia
5 affiliations
- 1The First Clinical Medical College, Ningxia Medical University, Yinchuan, China
- 2Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, China
- 3Ningxia Human Sperm Bank, General Hospital of Ningxia Medical University, Yinchuan, China
- 4Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, China
- 5Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan, China
Abstract
IntroductionNon-obstructive azoospermia (NOA) is a severe male infertility disorder caused by spermatogenic failure, and UTF1 is critical for maintaining undifferentiated spermatogonia and regulating germ cell development. This study aimed to explore the role of UTF1-related spermatogenic dysfunction in NOA and identify potential diagnostic biomarkers.MethodsWe integrated NOA transcriptomic datasets with single-cell RNA sequencing (scRNA-seq) data from Utf1 conditional knockout and normal mouse testes. Bioinformatic analyses and machine learning were applied to screen biomarkers, while functional enrichment, immune infiltration, cell-cell communication, and pseudotime trajectory analyses were performed together with histological validation in Utf1-deficient testes.ResultsSpermatogonia, Sertoli cells, and spermatids were identified as key cell populations. ACTRT2 and AKAP4 were confirmed as consistently downregulated NOA biomarkers and were integrated into a well-calibrated nomogram. These two genes were associated with cytoskeletal remodeling and meiotic regulation. NOA was also characterized by altered immune infiltration and cell-cell communication, whereas Utf1 deficiency impaired testicular development and spermatogenesis.DiscussionCollectively, UTF1 deficiency was closely associated with spermatogenic dysfunction and microenvironmental remodeling in NOA, while ACTRT2 and AKAP4 might serve as potential diagnostic biomarkers of this process. These findings provide new insights into the molecular basis of NOA and may support future disease stratification and targeted intervention strategies.
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BibTeX
@article{yu2026integrated,
title = {{Integrated single-cell and bulk transcriptomic analyses reveal UTF1-associated spermatogenic dysfunction and identify ACTRT2 and AKAP4 as biomarkers in non-obstructive azoospermia}},
author = {Jin Yu and Mingming Li and Yue Zhou and Hekun Liu and Chengbin Pei and Lianghong Ma and Lianghong Ma and Lianghong Ma and Lianghong Ma},
journal = {Frontiers in Genetics},
year = {2026},
month = oct,
doi = {10.3389/fgene.2026.1975399},
url = {https://doi.org/10.3389/fgene.2026.1975399},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated single-cell and bulk transcriptomic analyses reveal UTF1-associated spermatogenic dysfunction and identify ACTRT2 and AKAP4 as biomarkers in non-obstructive azoospermia
AU - Jin Yu
AU - Mingming Li
AU - Yue Zhou
AU - Hekun Liu
AU - Chengbin Pei
AU - Lianghong Ma
AU - Lianghong Ma
AU - Lianghong Ma
AU - Lianghong Ma
PY - 2026
DA - 2026/10/26
JO - Frontiers in Genetics
DO - 10.3389/fgene.2026.1975399
UR - https://doi.org/10.3389/fgene.2026.1975399
AB - IntroductionNon-obstructive azoospermia (NOA) is a severe male infertility disorder caused by spermatogenic failure, and UTF1 is critical for maintaining undifferentiated spermatogonia and regulating germ cell development. This study aimed to explore the role of UTF1-related spermatogenic dysfunction in NOA and identify potential diagnostic biomarkers.MethodsWe integrated NOA transcriptomic datasets with single-cell RNA sequencing (scRNA-seq) data from Utf1 conditional knockout and normal mouse testes. Bioinformatic analyses and machine learning were applied to screen biomarkers, while functional enrichment, immune infiltration, cell-cell communication, and pseudotime trajectory analyses were performed together with histological validation in Utf1-deficient testes.ResultsSpermatogonia, Sertoli cells, and spermatids were identified as key cell populations. ACTRT2 and AKAP4 were confirmed as consistently downregulated NOA biomarkers and were integrated into a well-calibrated nomogram. These two genes were associated with cytoskeletal remodeling and meiotic regulation. NOA was also characterized by altered immune infiltration and cell-cell communication, whereas Utf1 deficiency impaired testicular development and spermatogenesis.DiscussionCollectively, UTF1 deficiency was closely associated with spermatogenic dysfunction and microenvironmental remodeling in NOA, while ACTRT2 and AKAP4 might serve as potential diagnostic biomarkers of this process. These findings provide new insights into the molecular basis of NOA and may support future disease stratification and targeted intervention strategies.
SN - 1664-8021
ER -