Loss of α-catenin in germ cells impairs spermatogenesis and flagellar function associated with teratozoospermia
4 affiliations
- 1Genetic Diseases Key Laboratory of Sichuan Province, Department of Medical Genetics, Department of Laboratory Medicine, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China
- 2Department of Laboratory Medicine, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu, Sichuan 610041, China
- 3Sichuan-Chongqing Joint Key Laboratory of Pathology and Laboratory Medicine, Jinfeng Laboratory, Chongqing 401329, China
- 4Department of Ophthalmology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China
Abstract
Infertility affects approximately 10%–20% of couples worldwide, with male factors accounting for roughly half of all cases. Teratozoospermia, defined by the occurrence of abnormally shaped sperm, is a significant contributor to male infertility. Here, by analyzing a publicly available RNA array dataset comparing teratozoospermia patients and normal controls, we uncovered disrupted adherens junction (AJ)-associated signaling and defective spermatogenesis within germ cells of teratozoospermia patients. In adherens junctions (AJs), α-catenin (CTNNA1) anchors the cadherin-catenin complex to the actin cytoskeleton and regulates actin organization, but its role in germ cell development and sperm function remains unknown. We generated a germ cell-specific Ctnna1 conditional knockout mouse model (Ctnna1cKO). Homozygous Ctnna1-deficient mice exhibited male infertility with abnormal structure and function of spermatozoa. Single-cell RNA sequencing of control and Ctnna1cKO testes revealed an accumulation of spermatogonia with impaired differentiation and abnormal acrosome structure in Ctnna1-deficient mice, likely caused by disrupted splicing and meiotic processes through dysregulated vinculin. Additionally, loss of α-catenin disrupted both direct and indirect interactions between spermatogenic cells and Sertoli cells, as evidenced by N-cadherin internalization that mediates their adhesion and by reduced Cyclophilin A/CD147 paracrine signaling essential for spermatogenesis. Mechanistically, loss of α-catenin results in disorganization of the α-catenin/vinculin/N-cadherin complex, leading to defective cell-cell interactions and impairment of spermatogenesis. Collectively, our study establishes α-catenin as a critical regulator of spermatogenesis and germ cell development and highlights its potential as a prognostic biomarker and therapeutic target for male infertility, particularly teratozoospermia.
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BibTeX
@article{ha2026loss,
title = {{Loss of α-catenin in germ cells impairs spermatogenesis and flagellar function associated with teratozoospermia}},
author = {Xu Ha and Shu-Jin Li and Ru-Lian Zhao and Lan-Yao Yang and Yun-Qi He and Li Peng and Li-Ting Lv and Xian-Jun Zhu and Mu Yang and Zheng-Lin Yang},
journal = {Zoological Research},
year = {2026},
month = sep,
doi = {10.24272/j.issn.2095-8137.2025.530},
url = {https://doi.org/10.24272/j.issn.2095-8137.2025.530},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Loss of α-catenin in germ cells impairs spermatogenesis and flagellar function associated with teratozoospermia
AU - Xu Ha
AU - Shu-Jin Li
AU - Ru-Lian Zhao
AU - Lan-Yao Yang
AU - Yun-Qi He
AU - Li Peng
AU - Li-Ting Lv
AU - Xian-Jun Zhu
AU - Mu Yang
AU - Zheng-Lin Yang
PY - 2026
DA - 2026/09/18
JO - Zoological Research
DO - 10.24272/j.issn.2095-8137.2025.530
UR - https://doi.org/10.24272/j.issn.2095-8137.2025.530
AB - Infertility affects approximately 10%–20% of couples worldwide, with male factors accounting for roughly half of all cases. Teratozoospermia, defined by the occurrence of abnormally shaped sperm, is a significant contributor to male infertility. Here, by analyzing a publicly available RNA array dataset comparing teratozoospermia patients and normal controls, we uncovered disrupted adherens junction (AJ)-associated signaling and defective spermatogenesis within germ cells of teratozoospermia patients. In adherens junctions (AJs), α-catenin (CTNNA1) anchors the cadherin-catenin complex to the actin cytoskeleton and regulates actin organization, but its role in germ cell development and sperm function remains unknown. We generated a germ cell-specific Ctnna1 conditional knockout mouse model (Ctnna1cKO). Homozygous Ctnna1-deficient mice exhibited male infertility with abnormal structure and function of spermatozoa. Single-cell RNA sequencing of control and Ctnna1cKO testes revealed an accumulation of spermatogonia with impaired differentiation and abnormal acrosome structure in Ctnna1-deficient mice, likely caused by disrupted splicing and meiotic processes through dysregulated vinculin. Additionally, loss of α-catenin disrupted both direct and indirect interactions between spermatogenic cells and Sertoli cells, as evidenced by N-cadherin internalization that mediates their adhesion and by reduced Cyclophilin A/CD147 paracrine signaling essential for spermatogenesis. Mechanistically, loss of α-catenin results in disorganization of the α-catenin/vinculin/N-cadherin complex, leading to defective cell-cell interactions and impairment of spermatogenesis. Collectively, our study establishes α-catenin as a critical regulator of spermatogenesis and germ cell development and highlights its potential as a prognostic biomarker and therapeutic target for male infertility, particularly teratozoospermia.
SN - 2095-8137
ER -