ArticleHuman molecular genetics2012
Altered LKB1/AMPK/TSC1/TSC2/mTOR signaling causes disruption of Sertoli cell polarity and spermatogenesis.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 82 citations in OpenAlex.
- Review
- The STK11 gene F354L mutation is associated with male spermatogenic dysfunction.Scientific reports · 2026Article
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Single-cell RNA sequencing uncovers abnormal Sertoli-cell elevation and testicular niche impairment in the transfemales's testis.Cell & bioscience · 2025Article
- Insights into targeting LKB1 in tumorigenesis.Genes & diseases · 2025Review
- Inactivation of JNK signalling results in polarity loss and cell senescence of Sertoli cell.Cell proliferation · 2025Article
- Semen Cryopreservation to Expand Male Fertility in Cancer Patients: Intracase Evaluation of Semen Quality.Journal of personalized medicine · 2023Article
- Defining Gene Function in Spermatogonial Stem Cells Through Conditional Knockout Approaches.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Genomic testing for copy number and single nucleotide variants in spermatogenic failure.Journal of assisted reproduction and genetics · 2022Article
- The PI3K/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?Histology and histopathology · 2022Review
- UHRF1 establishes crosstalk between somatic and germ cells in male reproduction.Cell death & disease · 2022Article
- Protein kinase A drives paracrine crisis and WNT4-dependent testis tumor in Carney complex.The Journal of clinical investigation · 2021Article
- MiR-181a Promotes Spermatogenesis by Targeting the S6K1 Pathway.International journal of stem cells · 2021Article
- Human Hsp90 cochaperones: perspectives on tissue-specific expression and identification of cochaperones with similar in vivo functions.Cell stress & chaperones · 2021Review
- Roles of AMP-Activated Protein Kinase (AMPK) in Mammalian Reproduction.Frontiers in cell and developmental biology · 2020Review
- Maternal energy insufficiency affects testicular development of the offspring in a swine model.Scientific reports · 2019Article
- AMPK Function in Mammalian Spermatozoa.International journal of molecular sciences · 2018Review
- MicroRNA-7450 regulates non-thermal plasma-induced chicken Sertoli cell apoptosis via adenosine monophosphate-activated protein kinase activation.Scientific reports · 2018Article
- [Rictor/mTORC2 regulates blood-testis barrier and spermatogenesis in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis.Scientific reports · 2017Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Male patients with Peutz-Jeghers syndrome (PJS) have defective spermatogenesis and are at increased risk of developing Sertoli cell tumors. Mutations in the Liver Kinase B1 (LKB1/STK11) gene are associated with the pathogenesis of PJS and have been identified in non-PJS patients with sporadic testicular cancers. The mechanisms controlled by LKB1 signaling in Sertoli cell functions and testicular biology have not been described. We have conditionally deleted the Lkb1 gene (Lkb1(cko)) in somatic testicular cells to define the molecular mechanisms involved in the development of the testicular phenotype observed in PJS patients. Focal vacuolization in some of the seminiferous tubules was observed in 4-week-old mutant testes but germ cell development appeared to be normal. However, similar to PJS patients, we observed progressive germ cell loss and Sertoli cell only tubules in Lkb1(cko) testes from mice older than 10 weeks, accompanied by defects in Sertoli cell polarity and testicular junctional complexes and decreased activation of the MAP/microtubule affinity regulating and focal adhesion kinases. Suppression of AMP kinase and activation of mammalian target of rapamycin (mTOR) signaling were also observed in Lkb1(cko) testes. Loss of Tsc1 or Tsc2 copies the progressive Lkb1(cko) phenotype, suggesting that dysregulated activation of mTOR contributes to the pathogenesis of the Lkb1(cko) testicular phenotype. Pten(cko) mice had a normal testicular phenotype, which could be explained by the comparative lack of mTOR activation detected. These studies describe the importance of LKB1 signaling in testicular biology and the possible molecular mechanisms driving the pathogenesis of the testicular defects observed in PJS patients.
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