ArticleNature communications2022
Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Docosahexaenoic acid alleviates Ornidazole toxicity related to spermatogenic dysfunction by modulating PPARγ-dependent ER-mitochondrial uncoupling.Science China. Life sciences · 2026Article
- Desert Hedgehog mediates stem Leydig cell differentiation through Ptch2/Gli1/Sf1 signaling axis.eLife · 2026Article
- Review
- LIPUS promotes stem leydig cells proliferation by up-regulating Wnt5a expression and delays male aging.Scientific reports · 2026Article
- An extracellular vesicle-mediated mitochondrial transfer network critical for testosterone synthesis.Nature cell biology · 2026Article
- High-fat diet leads to male reproductive dysfunction by disrupting lipid-droplet-mediated organelle crosstalk.Cellular & molecular biology letters · 2026Article
- The regulatory roles and therapeutic strategies of the solute carrier transporters in cancer metabolism.NPJ precision oncology · 2026Review
- Testicular macrophages: core immune regulators and emerging therapeutic targets in spermatogenic dysfunction.Frontiers in immunology · 2026Review
- Mitochondria-Localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- The Role of Environmental Endocrine Disruptors on Leydig Cell Death and Senescen.The world journal of men's health · 2025Review
- Research Progress on the Interaction Between SIRT1 and Mitochondrial Biochemistry in the Aging of the Reproductive System.Biology · 2025Review
- cGAMP-targeting injectable hydrogel system promotes periodontal restoration by alleviating cGAS-STING pathway activation.Bioactive materials · 2025Article
- Massage-Mimicking Nanosheets Mechanically Reorganize Inter-organelle Contacts to Restore Mitochondrial Functions in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanical signal-mediated mitochondria-endoplasmic reticulum contacts modulate Leydig cell testosterone biosynthesis during testis development.Molecular human reproduction · 2025Article
- Single-cell transcriptomic atlas of the human testis across the reproductive lifespan.Nature aging · 2025Article
- Efficient differentiation of human iPSCs into Leydig-like cells capable of long-term stable secretion of testosterone.Stem cell reports · 2025Article
- Testicular sex cord-stromal tumors in mice with constitutive activation of PI3K and loss of Pten.Carcinogenesis · 2025Article
- Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- GDF15 is associated with thyroid cancer progression and may modulate thyroid cancer cell senescence in a p53-dependent manner.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Male reproductive system ageing is closely associated with deficiency in testosterone production due to loss of functional Leydig cells, which are differentiated from stem Leydig cells (SLCs). However, the relationship between SLC differentiation and ageing remains unknown. In addition, active lipid metabolism during SLC differentiation in the reproductive system requires transportation and processing of substrates among multiple organelles, e.g., mitochondria and endoplasmic reticulum (ER), highlighting the importance of interorganelle contact. Here, we show that SLC differentiation potential declines with disordered intracellular homeostasis during SLC senescence. Mechanistically, loss of the intermediate filament Nestin results in lower differentiation capacity by separating mitochondria-ER contacts (MERCs) during SLC senescence. Furthermore, pharmacological intervention by melatonin restores Nestin-dependent MERCs, reverses SLC differentiation capacity and alleviates male reproductive system ageing. These findings not only explain SLC senescence from a cytoskeleton-dependent MERCs regulation mechanism, but also suggest a promising therapy targeting SLC differentiation for age-related reproductive system diseases.
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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.