State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Science, University of Chinese Academy of Science, Shanghai 200031, China
Published: July 2019
AI Article Synopsis
Article Abstract
Epigenetic regulation, including histone-to-protamine exchanges, controls spermiogenesis. However, the underlying mechanisms of this regulation are largely unknown. Here, we report that PHF7, a testis-specific PHD and RING finger domain-containing protein, is essential for histone-to-protamine exchange in mice. PHF7 is specifically expressed during spermiogenesis. PHF7 deletion results in male infertility due to aberrant histone retention and impaired protamine replacement in elongated spermatids. Mechanistically, PHF7 can simultaneously bind histone H2A and H3; its PHD domain, a histone code reader, can specifically bind H3K4me3/me2, and its RING domain, a histone writer, can ubiquitylate H2A. Thus, our study reveals that PHF7 is a novel E3 ligase that can specifically ubiquitylate H2A through binding H3K4me3/me2 prior to histone-to-protamine exchange.
BDE-209 exposure leads to male reproductive toxicity characterized by a decline in sperm quality, but the impact of autophagy in this process was not well understood.
The study evaluated the protective effects of trehalose (Tre), an autophagy inducer, on reproductive damage during sperm development (spermiogenesis) caused by BDE-209 using a mouse model.
Results showed that Tre improved various sperm qualities and reduced testicular damage, likely by restoring normal autophagy pathways via AMPK-ULK1 signaling, highlighting potential therapeutic targets for addressing male reproductive toxicity.
Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs).
Genetic studies have highlighted the importance of Phf7 in animal germline development, but the link between Phf7 mutations and male infertility needs more exploration.
Using Phf7 knockout mice, researchers confirmed that infertility is linked to genetic defects preventing the proper transition from histones to protamines and that immune pathways activated by endogenous retroviruses play a role.
The study identifies PPARα as a potential target for managing inflammation in the testis and suggests that the antioxidant astaxanthin could be a promising treatment for male infertility by restoring immune regulation affected by Phf7 loss.
Unique chromatin remodeling factors orchestrate dramatic changes in nuclear morphology during differentiation of the mature sperm head. A crucial step in this process is histone-to-protamine exchange, which must be executed correctly to avoid sperm DNA damage, embryonic lethality and male sterility. Here, we define an essential role for the histone methyltransferase DOT1L in the histone-to-protamine transition.
Department of Andrology, Center for Men's Health, Department of ART, Institute of Urologic Medical Center, Shanghai General Hospital, Shanghai Key Lab of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction: Oligoasthenoteratozoospermia (OAT) is a major cause of infertility in males. Only a few pathogenic genes of OAT have been clearly identified till now. A large number of OAT-affected cases remain largely unknown.
