Wenlong Zhao , Nihao Gu , Xueyuan Liu , Ningxin Qing , Jianzhong Sheng , Xianhua Lin , Hefeng Huang
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引用次数: 0
Abstract
Introduction
Mammalian sperm within a single ejaculate exhibit significant heterogeneity, with only a subset possessing the molecular characteristics required for successful fertilization. Identifying the defining traits of these high-fertility sperm remains an open question.
Objectives
To elucidate the molecular markers and mechanisms underlying the fertilization potential of sperm in both mice and humans, with a focus on the role of D-mannose.
Methods
Sperm morphology and functionality were analyzed using flow cytometry, biochemical assays, and immunofluorescence. Multi-omics analyses, including proteomics, metabolomics, and lipidomics, were conducted to identify distinct molecular signatures. Pharmacological interventions were employed to validate the role of key pathways, particularly Akt/mTOR signaling.
Results
Sperm with longer flagella demonstrated enhanced motility, mitochondrial activity, and fertilization potential in both mice and humans. Multi-omics analyses revealed distinct molecular profiles in high-fertility sperm, characterized by specific proteins, lipids, and metabolites. Notably, D-mannose supplementation enhanced sperm motility and fertilization capacity, even in asthenozoospermic sperm, by activating the Akt/mTOR pathway. This effect was not replicated by D-glucose or ATP supplementation. Mechanistically, D-mannose bypassed glycolytic rate-limiting steps, increasing ATP production and promoting mitochondrial and acrosomal integrity.
Conclusion
This study identifies key molecular signatures of fertilization-competent sperm and highlights D-mannose as a novel modulator of sperm quality and function. These findings provide valuable insights into sperm biology and propose innovative therapeutic strategies for treating male infertility and optimizing assisted reproduction technologies.
期刊介绍:
Journal of Advanced Research (J. Adv. Res.) is an applied/natural sciences, peer-reviewed journal that focuses on interdisciplinary research. The journal aims to contribute to applied research and knowledge worldwide through the publication of original and high-quality research articles in the fields of Medicine, Pharmaceutical Sciences, Dentistry, Physical Therapy, Veterinary Medicine, and Basic and Biological Sciences.
The following abstracting and indexing services cover the Journal of Advanced Research: PubMed/Medline, Essential Science Indicators, Web of Science, Scopus, PubMed Central, PubMed, Science Citation Index Expanded, Directory of Open Access Journals (DOAJ), and INSPEC.