ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
HSF5 Deficiency Causes Male Infertility Involving Spermatogenic Arrest at Meiotic Prophase I in Humans and Mice.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- WFS1 Deficiency Impairs PIAS4-Associated SUMOylation and Increases Ubiquitin-Mediated Spermatogenesis-Related Protein Degradation Leading to Testicular Male Infertility.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A novel hemizygous missense variant in the BEND2 gene is associated with nonobstructive azoospermia.Asian journal of andrology · 2026Article
- Circadian Disruption Is Associated with Elevated Whole-Semen mtDNA Copy Number and ImplicatesInternational journal of molecular sciences · 2026Article
- Pervasive relaxed selection on spermatogenesis genes coincident with the evolution of polygyny in gorillas.eLife · 2026Article
- SOX30 Governs Synaptonemal Complex Assembly and Homologous Recombination in Male Meiosis.Cell proliferation · 2026Article
- Testicular mRNA-LNP Delivery: A Novel Therapy for Genetic Spermatogenic Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The intricate dance of RNA-binding proteins: unveiling the mechanisms behind male infertility.Human reproduction update · 2026Review
- Heat shock proteins in male infertility: recent advances and clinical implications.Frontiers in cell and developmental biology · 2026Review
- Statistical methods to disentangle genetic effects influencing infertility and early fetal viability with a genome-wide application.PLoS genetics · 2025Article
- Therapeutic Repair of Sperm Quality Decline Caused by Polytetrafluoroethylene.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Heat shock proteins in hypothermia: a review.Frontiers in molecular biosciences · 2025Review
- HSF5 Deficiency Causes Male Infertility Involving Spermatogenic Arrest at Meiotic Prophase I in Humans and Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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22 authors.
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Abstract
Meiosis is a specialized cell division process that generates gametes for sexual reproduction. However, the factors and underlying mechanisms involving meiotic progression remain largely unknown, especially in humans. Here, it is first showed that HSF5 is associated with human spermatogenesis. Patients with a pathogenic variant of HSF5 are completely infertile. Testicular histologic findings in the patients reveal rare postmeiotic germ cells resulting from meiotic prophase I arrest. Hsf5 knockout (KO) mice confirms that the loss of HSF5 causes defects in meiotic recombination, crossover formation, sex chromosome synapsis, and sex chromosome inactivation (MSCI), which may contribute to spermatocyte arrest at the late pachytene stage. Importantly, spermatogenic arrest can be rescued by compensatory HSF5 adeno-associated virus injection into KO mouse testes. Mechanistically, integrated analysis of RNA sequencing and chromatin immunoprecipitation sequencing data revealed that HSF5 predominantly binds to promoters of key genes involved in crossover formation (e.g., HFM1, MSH5 and MLH3), synapsis (e.g., SYCP1, SYCP2 and SYCE3), recombination (TEX15), and MSCI (MDC1) and further regulates their transcription during meiotic progression. Taken together, the study demonstrates that HSF5 modulates the transcriptome to ensure meiotic progression in humans and mice. These findings will aid in genetic diagnosis of and potential treatments for male infertility.
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