ReviewFrontiers in cell and developmental biology2019
Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals.
Review in Frontiers in cell and developmental biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Novel male contraceptives.Future science OA · 2026Review
- Mussel Spermatozoa Express a Specific Isoform of the Catalytic Subunit of cAMP-Dependent Protein Kinase.Molecular reproduction and development · 2026Article
- Physiological basis of contraceptive function of a GSK3α-selective inhibitor, manifested during epididymal sperm maturation.Molecular human reproduction · 2026Article
- Sperm Proteomics and Phosphoproteomics: High-Throughput Methods Tailored to Gain Insight into Sperm Cell Signaling Pathways.Methods in molecular biology (Clifton, N.J.) · 2026Article
- ANKEF1 is a key axonemal component essential for murine sperm motility and male fertility.eLife · 2025Article
- A special perspective on human fertilization: The role of sperm capacitation proteins and channels: A narrative review.International journal of reproductive biomedicine · 2025Review
- Sodium butyrate promotes synthesis of testosterone and meiosis of hyperuricemic male mice.Scientific reports · 2025Article
- Whole-genome bisulfite sequencing of X and Y sperm in Holstein bulls reveals differences in autosomal methylation status.BMC genomics · 2025Article
- PP1γ1 is unable to substitute for the mammal-specific PP1γ2 isoform to support male fertility and sperm function.Reproduction (Cambridge, England) · 2025Article
- Boar Sperm Motility Assessment Using Computer-Assisted Sperm Analysis: Current Practices, Limitations, and Methodological Challenges.Animals : an open access journal from MDPI · 2025Review
- Calcium Channels and Modulators as Potential Therapeutic Targets for Contraceptives and Male Fertility: A Scoping Review.Open access journal of contraception · 2025Review
- Comparative Proteomic Identification of Ram Sperm before and after In Vitro Capacitation.Animals : an open access journal from MDPI · 2024Article
- FromiScience · 2024Article
- Control of intracellular pH and bicarbonate by CONature communications · 2023Article
- Identification of IQCH as a calmodulin-associated protein required for sperm motility in humans.iScience · 2023Article
- Comparative characteristics between calyculin A-induced and thimerosal-induced hyperactivation of cryopreserved bovine spermatozoa.The Journal of reproduction and development · 2023Article
- cAMP controls the balance between dormancy and activation of primordial follicles in mouse ovaries.PNAS nexus · 2023Article
- Effect of C-Type Natriuretic Peptide (CNP) on Spermatozoa Maturation in Adult Rat Epididymis.Current issues in molecular biology · 2023Article
- Capacitation induces changes in metabolic pathways supporting motility of epididymal and ejaculated sperm.Frontiers in cell and developmental biology · 2023Article
- PP1, PP2A and PP2B Interplay in the Regulation of Sperm Motility: Lessons from Protein Phosphatase Inhibitors.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
In mammals, motility and fertilizing ability of spermatozoa develop during their passage through the epididymis. After ejaculation, sperm undergo capacitation and hyperactivation in the female reproductive tract - a motility transition that is required for sperm penetration of the egg. Both epididymal initiation of sperm motility and hyperactivation are essential for male fertility. Motility initiation in the epididymis and sperm hyperactivation involve changes in metabolism, cAMP (cyclic adenosine mono-phosphate), calcium and pH acting through protein kinases and phosphatases. Despite this knowledge, we still do not understand, in biochemical terms, how sperm acquire motility in the epididymis and how motility is altered in the female reproductive tract. Recent data show that the sperm specific protein phosphatase PP1γ2, glycogen synthase kinase 3 (GSK3), and the calcium regulated phosphatase calcineurin (PP2B), are involved in epididymal sperm maturation. The protein phosphatase PP1γ2 is present only in testis and sperm in mammals. PP1γ2 has a isoform-specific requirement for normal function of mammalian sperm. Sperm PP1γ2 is regulated by three proteins - inhibitor 2, inhibitor 3 and SDS22. Changes in phosphorylation of these three inhibitors and their binding to PP1γ2 are involved in initiation and activation of sperm motility. The inhibitors are phosphorylated by protein kinases, one of which is GSK3. The isoform GSK3α is essential for epididymal sperm maturation and fertility. Calcium levels dramatically decrease during sperm maturation and initiation of motility suggesting that the calcium activated sperm phosphatase (PP2B) activity also decreases. Loss of PP2B results in male infertility due to impaired sperm maturation in the epididymis. Thus the three signaling enzymes PP1γ2, GSK3, and PP2B along with the documented PKA (protein kinase A) have key roles in sperm maturation and hyperactivation. Significantly, all these four signaling enzymes are present as specific isoforms only in placental mammals, a testimony to their essential roles in the unique aspects of sperm function in mammals. These findings should lead to a better biochemical understanding of the basis of male infertility and should lead to novel approaches to a male contraception and managed reproduction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.