Journal Article

DZNE-2020-02727

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The nuclear form of glutathione peroxidase 4 is associated with sperm nuclear matrix and is required for proper paternal chromatin decondensation at fertilization.

Puglisi, R. ; Maccari, I. ; Pipolo, S. ; Conrad, M.DZNE* ; Mangia, F. ; Boitani, C. (Corresponding author)

2012
Wiley-Liss59471 New York, NY [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1002/jcp.22857

Abstract: The nuclear isoform of the selenoprotein Phospholipid Hydroperoxide Glutathione Peroxidase (nGPx4) is expressed in haploid male germ cells, contains several cysteines and is able to oxidize protein thiols, besides glutathione. In this study we have investigated the subnuclear localization of this isoform in isolated mouse male germ cells at different steps of maturation. Immunoblotting and confocal microscopy analyses of subnuclear fractions showed that nGPx4 is localized to the nuclear matrix together with well known markers of this subnuclear compartment like lamin B and topoisomerase IIβ at all stages of germ cell differentiation. The peculiar nGPx4 distribution was confirmed by both biochemical and morphological analyses of COS-1 cells overexpressing Flag-tagged nGPx4. To test the functional role of nGPx4 in the process of chromatin assembly, sperm isolated from the caput and the cauda epididymides of wild-type (WT) and genetically deficient in nGPx4 (nGPx4-KO) mice were analyzed in an in vitro chromatin decondensation assay. Results showed that sperm from nGPx4-KO mice were more prone to decondense than those from WT mice at all stages of epididymal maturation, providing conclusive evidence that nGPx4 is required for a correct sperm chromatin compaction. We next addressed the issue of whether the lack of nGPx4 impacts on early events occurring at fertilization. Indeed, in vitro fertilization experiments showed an acceleration of sperm chromatin dispersion in oocytes fertilized by nGpx4-KO sperm compared with control. Overall these data indicate that the absence of nGPx4 leads to sperm nuclear matrix/chromatin instability that may negatively affect the embryo development.

Keyword(s): Animals (MeSH) ; COS Cells (MeSH) ; Chlorocebus aethiops (MeSH) ; Chromatin Assembly and Disassembly: physiology (MeSH) ; Chromosomal Instability: physiology (MeSH) ; Embryonic Development: physiology (MeSH) ; Epididymis: cytology (MeSH) ; Epididymis: enzymology (MeSH) ; Female (MeSH) ; Fertilization: physiology (MeSH) ; Fertilization in Vitro (MeSH) ; Glutathione Peroxidase: deficiency (MeSH) ; Glutathione Peroxidase: genetics (MeSH) ; Glutathione Peroxidase: metabolism (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Nuclear Matrix: enzymology (MeSH) ; Oocytes: physiology (MeSH) ; Phospholipid Hydroperoxide Glutathione Peroxidase (MeSH) ; Recombinant Proteins: genetics (MeSH) ; Recombinant Proteins: metabolism (MeSH) ; Spermatogenesis: physiology (MeSH) ; Spermatozoa: enzymology (MeSH) ; Spermatozoa: physiology (MeSH) ; Transfection (MeSH) ; Recombinant Proteins ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Glutathione Peroxidase

---

Contributing Institute(s):

1. Genome Engineering (AG Wurst)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2012

---

Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

---