ArticleBiology of reproduction2015
Targeted disruption of glycogen synthase kinase 3A (GSK3A) in mice affects sperm motility resulting in male infertility.
Article in Biology of reproduction, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- Physiological basis of contraceptive function of a GSK3α-selective inhibitor, manifested during epididymal sperm maturation.Molecular human reproduction · 2026Article
- Spatio-temporal dynamics of autophagy-associated genes in macrophage-driven atherosclerosis: an integrated omics and experimental study.Frontiers in endocrinology · 2026Article
- Article
- Human asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.Andrology · 2025Review
- PP1γ1 is unable to substitute for the mammal-specific PP1γ2 isoform to support male fertility and sperm function.Reproduction (Cambridge, England) · 2025Article
- Article
- CCDC28A deficiency causes sperm head defects, reduced sperm motility and male infertility in mice.Cellular and molecular life sciences : CMLS · 2024Article
- Regulation of Phosphorylation of Glycogen Synthase Kinase 3α and the Correlation with Sperm Motility in Human.The world journal of men's health · 2024Article
- Novel underlying genetic markers for asthenozoospermia due to abnormal spermatogenesis and reproductive organ inflammation.Experimental and therapeutic medicine · 2024Article
- Differential role of bovine serum albumin and HCO3- in the regulation of GSK3 alpha during mouse sperm capacitation.Molecular human reproduction · 2024Article
- Inhibition of mitochondrial cyclophilin D, a downstream target of glycogen synthase kinase 3α, improves sperm motility.Reproductive biology and endocrinology : RB&E · 2024Article
- Role of the Glycogen Synthase Kinase 3-Cyclic AMP/Protein Kinase A in the Immobilization of Human Sperm by Tideglusib.Reproductive sciences (Thousand Oaks, Calif.) · 2023Article
- Glycogen Synthase Kinase-3 Isoform Variants and Their Inhibitory Phosphorylation in Human Testes and Spermatozoa.The world journal of men's health · 2023Article
- Sperm Phosphoproteome: Unraveling Male Infertility.Biology · 2022Review
- Environmental factors in declining human fertility.Nature reviews. Endocrinology · 2022Review
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- Quantitative phosphoproteomics reveals GSK3A substrate network is involved in the cryodamage of sperm motility.Bioscience reports · 2021Article
- Mouse and Fly Sperm Motility Changes Differently under Modelling Microgravity.Current issues in molecular biology · 2021Article
- A multiplier peroxiporin signal transduction pathway powers piscine spermatozoa.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer.Biomolecules · 2020Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The signaling enzyme glycogen synthase kinase 3 (GSK3) exists as two isoforms-GSK3A and GSK3B. Protein phosphorylation by GSK3 has important signaling roles in several cells. In our past work, we found that both isoforms of GSK3 are present in mouse sperm and that catalytic GSK3 activity correlates with motility of sperm from several species. Here, we examined the role of Gsk3a in male fertility using a targeted gene knockout (KO) approach. The mutant mice are viable, but have a male infertility phenotype, while female fertility is unaffected. Testis weights of Gsk3a(-/-) mice are normal and sperm are produced in normal numbers. Although spermatogenesis is apparently unimpaired, sperm motility parameters in vitro are impaired. In addition, the flagellar waveform appears abnormal, characterized by low amplitude of flagellar beat. Sperm ATP levels were lower in Gsk3a(-/-) mice compared to wild-type animals. Protein phosphatase PP1 gamma2 protein levels were unaltered, but its catalytic activity was elevated in KO sperm. Remarkably, tyrosine phosphorylation of hexokinase and capacitation-associated changes in tyrosine phosphorylation of proteins are absent or significantly lower in Gsk3a(-/-) sperm. The GSK3B isoform was present and unaltered in testis and sperm of Gsk3a(-/-) mice, showing the inability of GSK3B to substitute for GSK3A in this context. Our studies show that sperm GSK3A is essential for male fertility. In addition, the GSK3A isoform, with its highly conserved glycine-rich N terminus in mammals, may have an isoform-specific role in its requirement for normal sperm motility and fertility.
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