Chromatin Remodeling in Spermatids: A Sensitive Step for the Genetic Integrity of the Male Gamete

Laberge, Rémi-Martin; Boissonneault, Guylain

doi:10.1080/014850190518134

Cited by 47 publications

(29 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, we observed a severe decrease in DNA fragmentation when spermatids were incubated with two topoII inhibitors, namely etoposide and suramin [Laberge and Boissonneault 2005a]. Using confocal microscopy, we recently confirmed the presence of topoisomerase IIb (TOP2B, topoIIb) distributed in foci during steps 9 to 13 of mouse spermiogenesis but did not observe the presence of the a isoform at these steps [Leduc et al unpublished results].…”

Section: Endogenous Dna Fragmentation and Repair As Part Of Normal Spsupporting

confidence: 55%

“…The origin of DNA fragmentation in human spermatozoa remains unknown and multiple sources have been proposed including abortive apoptosis, abnormal chromatin packaging, generation of reactive oxygen species and premature release of spermatids from Sertoli cells [Muratori et al 2006;Oliva 2006;Sakkas et al 2002;Tesarik et al 2006]. We have also proposed that the DNA fragmentation detected in mature spermatozoa may originate from the persistence of the transient DNA strand breaks observed at mid-spermiogenesis steps [Laberge and Boissonneault 2005a]. These transient DNA strand breaks appear to be part of the normal differentiation program of the spermatids and are produced to either support the important change in DNA topology or as a result of a transient exposure to endogenous nuclease during the chromatin remodeling.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Leduc¹,

Nkoma²,

Boissonneault³

2008

Systems Biology in Reproductive Medicine

View full text Add to dashboard Cite

This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids. We propose that alterations in the chromatin remodeling steps or DNA repair in elongating spermatids may lead to persistent DNA breaks. This vulnerable step of spermiogenesis may provide a clue to the etiology of sperm DNA fragmentation associated with infertility in humans. This vulnerability is further emphasized given the haploid character of spermatids that must resolve programmed double-stranded breaks by an error-prone DNA repair mechanism. Therefore, spermiogenesis has probably been overlooked as an important source of genetic instability.

show abstract

Section: Endogenous Dna Fragmentation and Repair As Part Of Normal Spsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Leduc¹,

Nkoma²,

Boissonneault³

2008

Systems Biology in Reproductive Medicine

View full text Add to dashboard Cite

show abstract

“…In mammalian male germ cells, DNA breaks occur during chromatin remodelling (Laberge and Boissonneault, 2005). Local nicks or breaks in the DNA might facilitate the opening of the chromatin structure and thus lead to the removal of histones and the incorporation of Tpl 94D , protamines and Mst77F.…”

Section: Dmentioning

confidence: 99%

Transition from a nucleosome-based to a protamine-based chromatin configuration during spermiogenesis inDrosophila

Rathke

Baarends

Jayaramaiah-Raja

et al. 2007

Journal of Cell Science

209

264

View full text Add to dashboard Cite

presence of the architectural protein CTCF, numerous DNA breaks, SUMO, UbcD6 and high content of ubiquitin, as well as testes-specific nuclear proteasomes at this time. Moreover, we report the first transition protein-like chromosomal protein, Tpl 94D, to be found in Drosophila. We propose that Tpl 94D -an HMG box protein -and the numerous DNA breaks facilitate chromatin unwinding as a prelude to protamine and Mst77F deposition. Finally, we show that histone modifications and removal are independent of protamine synthesis. ), the presence of CTCF and DNA breaks. We furthermore show that histone removal is independent of the presence of protamines. Both this histone removal and protamine accumulation are essential for transmission of the male genome to the oocyte, and therefore of fundamental importance for the persistence of species. ResultsCore histones and their variants are removed simultaneously from the DNA of spermatid nuclei prior to protamine accumulation In Drosophila melanogaster, sperm morphogenesis, i.e. from meiosis until sperm individualisation, lasts 3.5 days. After meiosis, the nucleus initially is round and then gradually changes its shape accompanied by reorganisation of the chromatin during the canoe stage (Jayaramaiah-Raja and Renkawitz-Pohl, 2005), resulting in sperm containing a slim nucleus in which the nuclear volume is decreased by a factor of 200 (for review see Fuller, 1993;Renkawitz-Pohl et al., 2005).In the work reported here we concentrated on post-meiotic sperm morphogenesis with particular focus on chromatin reorganisation from the nucleosomal-to the protamine-based structure, which is a dramatic switch. Previously, we have reported that the histone variant H2AvD-GFP vanishes at the canoe stage while protamines begin to accumulate simultaneously (Jayaramaiah-Raja and Renkawitz-Pohl, 2005). To analyse the timing of histone removal and protamine accumulation we brought protamine-eGFP and H2AvD-RFP (Clarkson and Saint, 1999) into one genetic background to enable a study in the same individual. We found that H2AvD-RFP disappeared before protamine-eGFP accumulation took place (data not shown). We then went on to immunostain testes of protamine-eGFP flies with an antibody recognising all histones. This antibody was raised against total histones of humans and detects all core histones and the linker histone H1 in mammals. As -in contrast to core histones -H1 is not well conserved between mammals and Drosophila, we presumably detect solely core histones with this antibody. Our findings show that core histones (Fig. 1A) are detectable up to the canoe stage whereas protamines start to be synthesised at the canoe stage (Fig. 1B) but with no apparent positional overlap. As the canoe stage is quite long, we defined the early canoe stage by the start of histone removal, and the late canoe stage by the start of protamine accumulation (see Fig. 1A-E, second and third columns). With histone H3.3, a further replacement variant is expressed in the testis and disappears in post-meiotic stages togethe...

show abstract

“…This is compatible with Knaapen et al (2005) (Knaapen et al, 2005) who recorded a rise in DNA fragmentation in adult rats and concluded that NaNO 2 induced DNA fragmentation due to oxidative stress. The rigid wrapping of chromatin, which depends on condensation and replacement of histones with Laberge and Boissonneault, 2005). Free radicals possess the capability to precisely injure sperm DNA by assaulting the purine and pyrimidine units and the backbone deoxyribose.…”

Section: Discussionmentioning

confidence: 99%

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

et al. 2017

View full text Add to dashboard Cite

Introduction: The present work aims to examine the possible role of stem cells on biochemical markers and histopathological alterations of hypoxia caused by sodium nitrite (NaNO 2 ) toxicity in testes of male rats. Methods: In this study, 96 adult male albino rats were divided into 6 groups (16 rats each). Group 1 (G1) was the control group and received distilled H 2 O. Group 2 (G2) received daily NaNO 2 (35 m/kg bwt/ day) via subcutaneous injection for 3 weeks. Group 3 (G3) received NaNO 2 for 2 weeks and were then injected once with 2*10 6 mesenchymal stem cells (MSCs) intravenously and sacrificed 4 weeks later. Group 4 (G4) received NaNO 2 for 2 weeks and were then injected with 2*10 6 MSCs followed by daily NaNO 2 injection for 1 week; rats in G4 were sacrificed 4 weeks from MSCs treatment. Group 5 (G5) rats were treated with NaNO 2 for 2 weeks and then left to recover for 4 weeks. Finally, Group 6 (G6) rats were treated with NaNO 2 for 3 weeks and left to recover for 3 weeks, after which point they were sacrificed. Results: The results showed that NaNO 2 caused oxidative damage and histopathological alterations in the rat testes, as well as increased the levels of testes malondialdehyde (MDA), nitric oxide (NO) and DNA fragmentation percentage (DNA F %). Moreover, NaNO 2 decreased the elevated activities of testes catalase (CAT) and total antioxidant activity (TAA), in comparison to the control group. The histological results illustrated different distortions, vacuolization and lipid accumulations in interlobular space as well as diminution of inter cellular germ cell layers, absence of Leydig cells, irregular basement membrane of tubule, and separation within spermatogenic cells. In

show abstract

Chromatin Remodeling in Spermatids: A Sensitive Step for the Genetic Integrity of the Male Gamete

Cited by 47 publications

References 54 publications

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Transition from a nucleosome-based to a protamine-based chromatin configuration during spermiogenesis inDrosophila

The potential role of mesenchymal stem cells in a hypoxia model induced by sodium nitrite in testes of male albino rats

Contact Info

Product

Resources

About