ArticleThe Journal of biological chemistry2015
Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Differentially expressed microRNAs in aneuploid preimplantation blastocysts: a systematic review.Frontiers in reproductive health · 2024Pooled it
- The core mechanism of hypertension-linked renal fibrosis: "RAAS-ROS-inflammation-fibrosis" axis.iScience · 2026Review
- Review
- How do lifestyle and environmental factors influence the sperm epigenome? Effects on sperm fertilising ability, embryo development, and offspring health.Clinical epigenetics · 2025Review
- Astrocyte Elevated Gene-1 Cys75Biochemistry · 2023Article
- Miat and interacting protein Metadherin maintain a stem-like niche to promote medulloblastoma tumorigenesis and treatment resistance.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance.Cancers · 2021Review
- Article
- MTDH/AEG-1 downregulation using pristimerin-loaded nanoparticles inhibits Fanconi anemia proteins and increases sensitivity to platinum-based chemotherapy.Gynecologic oncology · 2019Article
- Identification of high-confidence RNA regulatory elements by combinatorial classification of RNA-protein binding sites.Genome biology · 2017Article
- miRCat2: accurate prediction of plant and animal microRNAs from next-generation sequencing datasets.Bioinformatics (Oxford, England) · 2017Article
- The c.-190 C>A transversion in promoter region of protamine1 gene as a genetic risk factor for idiopathic oligozoospermia.Molecular biology reports · 2016Article
- The role of epigenetics in idiopathic male infertility.Journal of assisted reproduction and genetics · 2016Review
- Astrocyte Elevated Gene-1 (AEG-1) Regulates Lipid Homeostasis.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Increased expression of metadherin (MTDH, also known as AEG-1 and 3D3/LYRIC) has been associated with drug resistance, metastasis, and angiogenesis in a variety of cancers. However, the specific mechanisms through which MTDH is involved in these processes remain unclear. To uncover these mechanisms, we generated Mtdh knock-out mice via a targeted disruption of exon 3. Homozygous Mtdh knock-out mice are viable, but males are infertile. The homozygous male mice present with massive loss of spermatozoa as a consequence of meiotic failure. Accumulation of γ-H2AX in spermatocytes of homozygous Mtdh knock-out mice confirms an increase in unrepaired DNA breaks. We also examined expression of the DNA repair protein Rad18, which is regulated by MTDH at the post-transcriptional level. In testes from Mtdh exon 3-deficient mice, Rad18 foci were increased in the lumina of the seminiferous tubules. The Piwi-interacting RNA (piRNA)-interacting protein Mili was expressed at high levels in testes from Mtdh knock-out mice. Accordingly, genome-wide small RNA deep sequencing demonstrated altered expression of piRNAs in the testes of Mtdh knock-out mice as compared with wild type mice. In addition, we observed significantly reduced expression of microRNAs (miRNAs) including miR-16 and miR-19b, which are known to be significantly reduced in the semen of infertile men. In sum, our observations indicate a crucial role for MTDH in male fertility and the DNA repair mechanisms required for normal spermatogenesis.
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