ArticleDevelopment (Cambridge, England)2022
PFN4 is required for manchette development and acrosome biogenesis during mouse spermiogenesis.
Article in Development (Cambridge, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- A narrative review on the role of autophagy in male infertility-associated sperm abnormalities.Asian journal of andrology · 2026Review
- Male germ cell-specific deletion ofZoological research · 2026Article
- Pericentric inversion in chromosome 2 and their fertility issues: three cases report and literature review.Open medicine (Warsaw, Poland) · 2026Article
- Profilin and Its Isoforms: Unravelling the Functional Diversity Across Life Forms.Current protein & peptide science · 2026Review
- Profilin and Non-Canonical Wnt Signaling: Coordinating Cytoskeletal Dynamics from Development to Disease.Journal of developmental biology · 2025Review
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- Loss of Cep135 causes oligoasthenoteratozoospermia and male infertility in mice.Cellular and molecular life sciences : CMLS · 2025Article
- Homozygous deleterious variants in MYCBPAP induce asthenoteratozoospermia involving abnormal acrosome biogenesis, manchette structure and sperm tail assembly in humans and mice.Science China. Life sciences · 2025Article
- Immunofluorescence Staining of the Manchette and Developing Sperm Flagella in Mouse.Methods in molecular biology (Clifton, N.J.) · 2025Article
- St. John's wort extract Ze 117 alters the membrane fluidity of C6 glioma cells by influencing cellular cholesterol metabolism.Scientific reports · 2024Article
- The constructive and destructive impact of autophagy on both genders' reproducibility, a comprehensive review.Autophagy · 2023Review
- Review
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Profilin 4 (Pfn4) is expressed during spermiogenesis and localizes to the acrosome-acroplaxome-manchette complex. Here, we generated PFN4-deficient mice, with sperm displaying severe impairment in manchette formation. Interestingly, HOOK1 staining suggests that the perinuclear ring is established; however, ARL3 staining is disrupted, suggesting that lack of PFN4 does not interfere with the formation of the perinuclear ring and initial localization of HOOK1, but impedes microtubular organization of the manchette. Furthermore, amorphous head shape and flagellar defects were detected, resulting in reduced sperm motility. Disrupted cis- and trans-Golgi networks and aberrant production of proacrosomal vesicles caused impaired acrosome biogenesis. Proteomic analysis showed that the proteins ARF3, SPECC1L and FKBP1, which are involved in Golgi membrane trafficking and PI3K/AKT pathway, are more abundant in Pfn4-/- testes. Levels of PI3K, AKT and mTOR were elevated, whereas AMPK level was reduced, consistent with inhibition of autophagy. This seems to result in blockage of autophagic flux, which could explain the failure in acrosome formation. In vitro fertilization demonstrated that PFN4-deficient sperm is capable of fertilizing zona-free oocytes, suggesting a potential treatment for PFN4-related human infertility.
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