Mp01-14 the loss of histone reader phf7 leads to immune pathways activation via endogenous retroviruses during spermiogenesis

You have accessJournal of UrologyCME1 Apr 2023MP01-14 THE LOSS OF HISTONE READER PHF7 LEADS TO IMMUNE PATHWAYS ACTIVATION VIA ENDOGENOUS RETROVIRUSES DURING SPERMIOGENESIS Jianxing Cheng, Haocheng Lin, and Hui Jiang Jianxing ChengJianxing Cheng More articles by this author , Haocheng LinHaocheng Lin More articles by this author , and Hui JiangHui Jiang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003212.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Genetic studies have elucidated critical roles of the Phf7 in germline development in animals, but whether PHF7 is an actual disease gene in human infertility remains unknown. To investigate the role of PHF7 on infertility in humans and explore its mechanism. METHODS: The blood and testicular samples from azoospermia patients were collected and used for genome sequencing western blot and immunohistology. The Phf7 knockout mice model were established and used for animal study. RT-PCR, Immunohistology, and western blotting were used for phenotypic identification. Transcriptome of testicular haploid cells of Phf7 knockout mice were analyzed, and the differentially expressed ERV was further used for coverage analysis; Quantitative PCR and Western blot were performed to verification. Mouse germ cell lines GC-1 and GC-2 with ERV target knockouts were constructed for experiment in vitro. The chromatin accessibility and epigenetic changes of mouse testicular cells after Phf7 deletion were analyzed by ATAC-seq and ChIP-seq data. Targeted drugs for PPARα to treat Phf7 knockout mice. RESULTS: We report a germline mutation of human PHF7 in azoospermic patients and our findings to demonstrate that PHF7 is a potential etiological factor in non-obstructive azoospermic patients. By modeling such mutations in Phf7 knockout mice, we show that the genetic defects are directly responsible for male infertility that prevent histone-to-protamine exchange as previously reported. More importantly, the deficiency of spermatogenesis caused by the deletion of Phf7 through ERV-mediated activation of the immune pathway is a common mechanism of infertility. Moreover, PPARα is an emerging target of immunity and inflammation in testis which ERV suppressed, we further demonstrate that Astaxanthin is a promising drug for treating male infertility. CONCLUSIONS: Our findings identify Phf7 as a target in human infertility and reveal its role as an epigenetic reader, while the loss of Phf7 lead to immune pathways activation which can be rescued by PPARα agonist Astaxanthin. Source of Funding: This work was supported by: Natural Science Foundation of Beijing (General #7212134), National Natural Science Foundations of China (#81601272) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e7 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jianxing Cheng More articles by this author Haocheng Lin More articles by this author Hui Jiang More articles by this author Expand All Advertisement PDF downloadLoading ...