(278) The Loss of Histone Reader Phf7 Leads to Immune Pathways Activation via Endogenous Retroviruses During Spermiogenesis

Abstract

Abstract Introduction PHF7 has been identified as playing a crucial role in germline development in animals. However, its correlation with human infertility remains ambiguous. Objective To ascertain if a germline mutation in the human PHF7 gene correlates with azoospermic patients and to further determine if this mutation is a potential cause of non-obstructive azoospermia. Methods Genetic screening of azoospermic patients for PHF7 mutations. Using Phf7 knockout mice models to simulate the human mutation, aiming to validate if these mutations are directly responsible for male infertility. Investigating the role of endogenous retroviruses related to Phf7 deletion and its link to activating the immune pathway. Results A germline mutation of the human PHF7 gene was identified in azoospermic patients. In the Phf7 knockout mice model, male infertility was observed, specifically stemming from an inhibited histone-to-protamine exchange process. The absence of spermatogenesis due to the Phf7 deletion was found to be associated with the activation of the immune pathway, mediated by endogenous retroviruses. PPARα was identified as a significant factor in the testis, which is suppressed by endogenous retroviruses. Conclusions PHF7 is an essential gene associated with human infertility, particularly in non-obstructive azoospermic patients. Its role as an epigenetic reader became evident, and the absence of PHF7 leads to immune pathway activation. The study also highlighted that the PPARα agonist, Astaxanthin, holds promise as a therapeutic agent to treat male infertility resulting from PHF7 mutations. Disclosure No.