Kdm3a lysine demethylase is an Hsp90 client required for cytoskeletal rearrangements during spermatogenesis

The lysine demethylase Kdm3a (Jhdm2a, Jmjd1a) is required for male fertility, sex determination, and metabolic homeostasis through its nuclear role in chromatin remodeling. Many histone-modifying enzymes have additional nonhistone substrates, as well as nonenzymatic functions, contributing to the full spectrum of events underlying their biological roles. We present two Kdm3a mouse models that exhibit cytoplasmic defects that may account in part for the globozoospermia phenotype reported previously. Electron microscopy revealed abnormal acrosome and manchette and the absence of implantation fossa at the caudal end of the nucleus in mice without Kdm3a demethylase activity, which affected cytoplasmic structures required to elongate the sperm head. We describe an enzymatically active new Kdm3a isoform and show that subcellular distribution, protein levels, and lysine demethylation activity of Kdm3a depended on Hsp90. We show that Kdm3a localizes to cytoplasmic structures of maturing spermatids affected in Kdm3a mutant mice, which in turn display altered fractionation of beta-actin and gamma-tubulin. Kdm3a is therefore a multifunctional Hsp90 client protein that participates directly in the regulation of cytoskeletal components.Publisher PDFPeer reviewe

Tracking research trends and hotspots in sperm DNA fragmentation testing for the evaluation of male infertility: a scientometric analysis

BACKGROUND: This article describes the research trends in sperm DNA fragmentation (SDF) over the past 20 years (1999-2018) using a scientometric approach. METHODS: A stepwise approach was adopted to retrieve scientometric data (articles per year, authors, affiliations, journals, countries) from Scopus and analyze the publication pattern of SDF with reference to key areas of research in the field of Andrology. RESULTS: A total of 2121 articles were retrieved related to SDF. Our data revealed an increasing research trend in SDF (n = 33 to n = 173) over the past 20 years (R2 = 0.894). Most productive country in publications was the USA (n = 450), while Agarwal A. (n = 129) being the most productive author. Most of the articles in SDF were primarily focused on lifestyle (n = 157), asthenozoospermia (n = 135) and varicocele (130). Mechanistic studies on SDF were published twice as much as prognostic/diagnostic studies, with significant emphasis on oxidative stress. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was the most widely used technique to evaluate SDF. Publications on SDF related to assisted reproductive techniques also showed a linear increasing trend (R2 = 0.933). CONCLUSIONS: Our analysis revealed an increasing trend in SDF publications predominantly investigating lifestyle, asthenozoospermia and varicocele conditions with TUNEL being the most widely used technique. A substantial increase in research is warranted to establish SDF as prognostic/diagnostic parameter to evaluate clinical scenarios and ART outcomes