ArticleMolecular metabolism2024
Essential role of germ cell glycerol-3-phosphate phosphatase for sperm health, oxidative stress control and male fertility in mice.
Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inflammation-mediated effects of diabetes mellitus on male fertility: a systematic review and meta-analysis.Frontiers in endocrinology · 2025Pooled it
- FFAR4 Mediates High-Altitude Hypoxia-Induced Asthenozoospermia through Oxidative Stress and Mitochondrial Dysfunction: An Integrative Bioinformatics and Experimental Study.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Integrated metabolomic and transcriptomic analyses reveal that glutamine promotes chicken primordial germ cell‑like cell specification potentially through α-ketoglutarate.Animal bioscience · 2026Article
- Regulation of mitochondrial function during spermatogenesis and sperm maturation.Cellular & molecular biology letters · 2026Review
- Targeted metabolomics reveals the impact of glucose and pyruvate on energy metabolism and storage potential of stallion spermatozoa.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Comparative Analysis of Gut Microbiota and Metabolome of Captive Male Malayan Pangolins with Normal and Abnormal Reproduction.Animals : an open access journal from MDPI · 2026Article
- Exploration of Novel Markers in Tan Sheep Spermatogenesis.Animals : an open access journal from MDPI · 2026Article
- Glycerol and Glycerol-3-Phosphate: Multifaceted Metabolites in Metabolism, Cancer, and Other Diseases.Endocrine reviews · 2026Review
- Wu Zi Yan Zong Wan enhances sperm quality in boars by regulating spermatogenesis-related pathways and gut microbiota.Frontiers in veterinary science · 2026Article
- Suppressing Glycerol-3-phosphate Phosphatase and Enhancing Glycerol-3-Phosphate Shuttle Flux Crucial for High-Efficiency Fatty Acid Production in the Fast-Growing Oleaginous Schizochytrium.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Evaluation of Ambient Ozone Pollution Exposure on Mice Testicular Tissue: An Integrated Metabolomic and Transcriptomic Analysis.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Redox Regulation and Glucose Metabolism in the Stallion Spermatozoa.Antioxidants (Basel, Switzerland) · 2025Review
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13 authors.
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Abstract
objectivesObesity, diabetes and high-calorie diets are associated with defective sperm function and lowered male fertility. Mature spermatozoa primarily use fructose and glucose, and glucose and glycerol metabolism are important for sperm function. We recently discovered a novel mammalian enzyme, glycerol-3-phosphate (Gro3P) phosphatase (G3PP), and showed that it operates the glycerol shunt by hydrolyzing Gro3P to glycerol, and regulates glucose, lipid and energy metabolism in pancreatic β-cells and liver. We now observed that G3PP expression is the highest in the testis and spermatozoa, and investigated its role in male fertility.
methodsWe examined G3PP expression during spermatogenesis in mouse and assessed male fertility and spermatozoon function in conditional germ cell specific G3PP-KO (cG3PP-KO) mice and tamoxifen-inducible conditional germ cell G3PP-KO (icG3PP-KO) mice. We also determined the structural and metabolic parameters and oxidative stress in the spermatozoa from icG3PP-KO and control mice.
resultsG3PP expression in mouse spermatocytes and spermatids markedly increases during spermatogenesis. Male cG3PP-KO mice, in which germ cell G3PP is deleted from embryonic stage, are infertile due to dysfunctional sperm with reduced motility and capacitation, and elevated spontaneous acrosomal reaction and oxidative stress. However, icG3PP-KO male mice do not have altered fertility, due to the presence of ∼10% normal spermatozoa. icG3PP-KO spermatozoa display significantly reduced functionality and morphological and ultrastructural alterations. The icG3PP-KO spermatozoa show reduced glycerol production, elevated levels of Gro3P and reactive oxygen species (ROS), and oxidative stress that is associated with increased mitochondrial membrane potential.
conclusionsGerm cell G3PP deletion leads to the generation of spermatozoa that are functionally and structurally abnormal, likely due to the build-up of Gro3P that increases mitochondrial membrane potential, ROS, and oxidative stress and alters spermatozoa function. Overall, the results indicate that G3PP and the glycerol shunt are essential for normal spermatozoa function and male fertility.
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