ArticleReproductive biology and endocrinology : RB&E2023
Loss of ACTL7A causes small head sperm by defective acrosome-acroplaxome-manchette complex.
Article in Reproductive biology and endocrinology : RB&E, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Reduced and Mislocalized ACTL7A in Globozoospermia: Implications for Sperm Chromatin Integrity and Infertility.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Biallelic loss-of-function variants in DNAH12 cause inner dynein arm defects and sperm head abnormalities leading to male infertility.Journal of assisted reproduction and genetics · 2026Article
- A narrative review on the role of autophagy in male infertility-associated sperm abnormalities.Asian journal of andrology · 2026Review
- Clinical Features and PLCZ1 Gene Variants in Two Cases of Male Infertility: A Case Series and Literature Review.Molecular genetics & genomic medicine · 2026Review
- ELAPOR1 mediated vesicle traffic is required for acrosome biogenesis and male fertility in mice.Cellular and molecular life sciences : CMLS · 2026Article
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- Oxidative Stress-Associated Alterations in Sperm ACTL7A Expression and Function in Men With Varicocele.Oxidative medicine and cellular longevity · 2026Article
- Novel CYLC1 variants are associated with male infertility due to sperm head deformity.Journal of assisted reproduction and genetics · 2025Article
- Function of manchette and intra-manchette transport in spermatogenesis and male fertility.Cell communication and signaling : CCS · 2025Review
- 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
- Unraveling the mysteries of early embryonic arrest: genetic factors and molecular mechanisms.Journal of assisted reproduction and genetics · 2024Review
- Genetic etiological spectrum of sperm morphological abnormalities.Journal of assisted reproduction and genetics · 2024Review
- Bioinformatics Identification and Experimental Verification of Disulfidptosis-Related Genes in the Progression of Osteoarthritis.Biomedicines · 2024Article
- Inhibition of Prolactin Affects Epididymal Morphology by Decreasing the Secretion of Estradiol in Cashmere Bucks.Animals : an open access journal from MDPI · 2024Article
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Authors and funding
10 authors at 2 institutions in 1 country.
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Abstract
backgroundActin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms.
methodsNuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a.
resultsThe new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice.
conclusionsLoss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.
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