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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Characterization of Metabolic Patterns in Mouse Spermatogenesis and Its Clinical Implications in Humans

by
Jiachen Wang
1,†,
Mengqi Chen
1,†,
Ying Yao
1,
Mengyuan Zhu
2,
Yingtong Jiang
2,
Jiawei Duan
2,
Yan Yuan
1,
Laihua Li
1,
Minjian Chen
2,* and
Jiahao Sha
1,*
1
State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211166, China
2
Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2025, 26(3), 1001; https://doi.org/10.3390/ijms26031001
Submission received: 6 January 2025 / Revised: 21 January 2025 / Accepted: 23 January 2025 / Published: 24 January 2025
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Versions Notes

Abstract

Spermatogenesis is a complex process requiring precisely controlled metabolic adaptations. Although the genetic and cellular aspects of spermatogenesis have been extensively studied, the underlying metabolic mechanisms remain largely underexplored. In this study, we utilized STA-PUT technology to separate three key cell types involved in mouse spermatogenesis: pachytene spermatocytes (PAC), round spermatids (RS), and elongated spermatids (ES). A comprehensive untargeted metabolomic analysis revealed significant metabolic changes during spermatogenesis, such as reduced methylation-related metabolites and increased glycolytic intermediates and TCA cycle metabolites during ES. Moreover, metabolic differences between germ cells and somatic cells (Leydig and Sertoli cells) were highlighted, particularly in steroidogenesis and lipid metabolism. To investigate clinical relevance, we analyzed human seminal plasma. Samples from individuals with azoospermia displayed significant metabolic abnormalities, including reduced methionine, tryptophan, and arginine, which play vital roles in sperm development. Pathway enrichment analysis revealed disturbances in the metabolism of nucleotide, amino acid, and energy in azoospermia, suggesting potential biomarkers of male infertility. Our findings provide a comprehensive metabolic profile of spermatogenesis and suggest that metabolic alterations may be significant contributors to male infertility, particularly in cases of azoospermia.
Keywords: metabolomics; spermatogenesis; Leydig cells; Sertoli cells; azoospermia; seminal plasma metabolomics; spermatogenesis; Leydig cells; Sertoli cells; azoospermia; seminal plasma

Share and Cite

MDPI and ACS Style

Wang, J.; Chen, M.; Yao, Y.; Zhu, M.; Jiang, Y.; Duan, J.; Yuan, Y.; Li, L.; Chen, M.; Sha, J. Characterization of Metabolic Patterns in Mouse Spermatogenesis and Its Clinical Implications in Humans. Int. J. Mol. Sci. 2025, 26, 1001. https://doi.org/10.3390/ijms26031001

AMA Style

Wang J, Chen M, Yao Y, Zhu M, Jiang Y, Duan J, Yuan Y, Li L, Chen M, Sha J. Characterization of Metabolic Patterns in Mouse Spermatogenesis and Its Clinical Implications in Humans. International Journal of Molecular Sciences. 2025; 26(3):1001. https://doi.org/10.3390/ijms26031001

Chicago/Turabian Style

Wang, Jiachen, Mengqi Chen, Ying Yao, Mengyuan Zhu, Yingtong Jiang, Jiawei Duan, Yan Yuan, Laihua Li, Minjian Chen, and Jiahao Sha. 2025. "Characterization of Metabolic Patterns in Mouse Spermatogenesis and Its Clinical Implications in Humans" International Journal of Molecular Sciences 26, no. 3: 1001. https://doi.org/10.3390/ijms26031001

APA Style

Wang, J., Chen, M., Yao, Y., Zhu, M., Jiang, Y., Duan, J., Yuan, Y., Li, L., Chen, M., & Sha, J. (2025). Characterization of Metabolic Patterns in Mouse Spermatogenesis and Its Clinical Implications in Humans. International Journal of Molecular Sciences, 26(3), 1001. https://doi.org/10.3390/ijms26031001

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