{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Gonadotropin‐regulated testicular RNA helicase (GRTH), also known as DDX25, is a testis‐specific member of the DEAD‐box family of RNA helicases that plays a central role in post‐transcriptional regulation during spermatogenesis. Expressed in both germ cells (especially meiotic spermatocytes and round spermatids) and Leydig cells, DDX25 is produced as multiple isoforms via alternative translation start sites, in a hormone‐dependent manner."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In germ cells, DDX25 functions as a shuttle protein that mediates the nuclear export and cytoplasmic trafficking of specific mRNAs. It is a pivotal component of messenger ribonucleoprotein complexes that deliver these transcripts to the chromatoid body—a specialized, membrane‐less RNA processing center in round spermatids—where they are maintained until their delayed, stage‐specific translation into proteins required for chromatin remodeling (e.g., transition proteins and protamines) and spermatid elongation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " The phosphorylated (cytoplasmic) form of DDX25 is critical for its activity; disruption, as seen with mutations (e.g., R242H) that abolish phosphorylation, leads to diminished chromatoid body integrity, impaired mRNA translation, spermatogenic arrest at the round spermatid stage, and ultimately male infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " In addition, DDX25 influences other post‐transcriptional events such as the regulation of microRNA biogenesis that can modulate the translation of key spermatogenic factors"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and plays a modulatory role in Leydig cell steroidogenesis by impacting mRNA stability of steroidogenic regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Collectively, these studies underscore the multifunctional role of DDX25 in orchestrating mRNA transport, storage, and translation as well as in maintaining cell survival during spermatogenesis, thereby establishing its critical importance for male fertility and its potential as a target for nonhormonal male contraception."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yi Sheng, Chon-Hwa Tsai-Morris, Maria L Dufau "}, {"type": "b", "children": [{"type": "t", "text": "Cell-specific and hormone-regulated expression of gonadotropin-regulated testicular RNA helicase gene (GRTH/Ddx25) resulting from alternative utilization of translation initiation codons in the rat testis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M302411200"}], "href": "https://doi.org/10.1074/jbc.M302411200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12734186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12734186"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Chon-Hwa Tsai-Morris, Shi Lei, Qiong Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic organization and transcriptional analysis of gonadotropin-regulated testicular RNA helicase--GRTH/DDX25 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2004.02.004"}], "href": "https://doi.org/10.1016/j.gene.2004.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15094194"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15094194"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Chon-Hwa Tsai-Morris, Yi Sheng, Eric Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is essential for spermatid development and completion of spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0401855101"}], "href": "https://doi.org/10.1073/pnas.0401855101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15096601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15096601"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maria L Dufau, Raghuveer Kavarthapu "}, {"type": "b", "children": [{"type": "t", "text": "Gonadotropin Regulation Testicular RNA Helicase, Two Decades of Studies on Its Structure Function and Regulation From Its Discovery Opens a Window for Development of a Non-hormonal Oral Male Contraceptive."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Endocrinol (Lausanne) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fendo.2019.00576"}], "href": "https://doi.org/10.3389/fendo.2019.00576"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31555207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31555207"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maria L Dufau, Chon-Hwa Tsai-Morris "}, {"type": "b", "children": [{"type": "t", "text": "Gonadotropin-regulated testicular helicase (GRTH/DDX25): an essential regulator of spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Endocrinol Metab (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.tem.2007.09.001"}], "href": "https://doi.org/10.1016/j.tem.2007.09.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17889551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17889551"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Raghuveer Kavarthapu, Rajakumar Anbazhagan, Murugananthkumar Raju, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeted knock-in mice with a human mutation in GRTH/DDX25 reveals the essential role of phosphorylated GRTH in spermatid development during spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddz079"}], "href": "https://doi.org/10.1093/hmg/ddz079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31009948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31009948"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Rajakumar Anbazhagan, Raghuveer Kavarthapu, Steven L Coon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of Phosphorylated Gonadotropin-Regulated Testicular RNA Helicase (GRTH/DDX25) in the Regulation of Germ Cell Specific mRNAs in Chromatoid Bodies During Spermatogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2020.580019"}], "href": "https://doi.org/10.3389/fcell.2020.580019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33425888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33425888"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lisheng Dai, Chon-Hwa Tsai-Morris, Hisashi Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testis-specific miRNA-469 up-regulated in gonadotropin-regulated testicular RNA helicase (GRTH/DDX25)-null mice silences transition protein 2 and protamine 2 messages at sites within coding region: implications of its role in germ cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.282756"}], "href": "https://doi.org/10.1074/jbc.M111.282756"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22086916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22086916"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Chon-Hwa Tsai-Morris, Eitetsu Koh, Yi Sheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphism of the GRTH/DDX25 gene in normal and infertile Japanese men: a missense mutation associated with loss of GRTH phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gam065"}], "href": "https://doi.org/10.1093/molehr/gam065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17848414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17848414"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Murugananthkumar Raju, Raghuveer Kavarthapu, Rajakumar Anbazhagan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blockade of GRTH/DDX25 Phosphorylation by Cyclic Peptides Provides an Avenue for Developing a Nonhormonal Male Contraceptive."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.jmedchem.1c01201"}], "href": "https://doi.org/10.1021/acs.jmedchem.1c01201"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34601876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34601876"}]}]}]}