scholarly journals The activated ATM/p53 pathway promotes autophagy in response to oxidative stress-mediated DNA damage induced by Microcystin-LR in male germ cells

2021 ◽  
Vol 227 ◽  
pp. 112919
Author(s):  
Zhihui Tian ◽  
Haohao Liu ◽  
Xinghai Chen ◽  
Michael D. Losiewicz ◽  
Rui Wang ◽  
...  
Author(s):  
Paulina Nguyen-Powanda ◽  
Bernard Robaire

Abstract The efficiency of antioxidant defense system decreases with aging, thus resulting in high levels of reactive oxygen species (ROS) and DNA damage in spermatozoa. This damage can lead to genetic disorders in the offspring. There are limited studies investigating the effects of the total loss of antioxidants, such as superoxide dismutase-1 (SOD1), in male germ cells as they progress through spermatogenesis. In this study, we evaluated the effects of aging and removing SOD1 (in male germ cells of SOD1-null (Sod1−/−) mice) in order to determine the potential mechanism(s) of DNA damage in these cells. Immunohistochemical analysis showed an increase in lipid peroxidation and DNA damage in the germ cells of aged wild-type (WT) and Sod1−/− mice of all age. Immunostaining of OGG1, a marker of base excision repair (BER), increased in aged WT and young Sod1−/− mice. In contrast, immunostaining intensity of LIGIV and RAD51, markers of non-homologous end-joining (NHEJ) and homologous recombination (HR), respectively, decreased in aged and Sod1−/− mice. Gene expression analysis showed similar results with altered mRNA expression of these key DNA repair transcripts in pachytene spermatocytes and round spermatids of aged and Sod1−/− mice. Our study indicates that DNA repair pathway markers of BER, NHEJ, and HR are differentially regulated as a function of aging and oxidative stress in spermatocytes and spermatids, and aging enhances the repair response to increased oxidative DNA damage, whereas impairments in other DNA repair mechanisms may contribute to the increase in DNA damage caused by aging and the loss of SOD1.


2012 ◽  
Vol 129 (1) ◽  
pp. 135-145 ◽  
Author(s):  
Belinda J. Nixon ◽  
Simone J. Stanger ◽  
Brett Nixon ◽  
Shaun D. Roman

2019 ◽  
Author(s):  
Vijaya Charaka ◽  
Anjana Tiwari ◽  
Raj K Pandita ◽  
Clayton R Hunt ◽  
Tej K. Pandita

AbstractMaintaining genomic stability in a continually dividing cell population requires accurate DNA repair, especially in male germ cells. Repair and replication protein access to DNA, however, is complicated by chromatin compaction. The HP1β chromatin protein, encoded by Cbx1, is associated with chromatin condensation but its role in meiosis is not clear. To investigate the role of Cbx1 in male germ cells, we generated testis specific Cbx1 deficient transgenic mice by crossing Cbx1flox/flox (Cbx1f/f) mice with Stra8 Cre+/− mice. Loss of Cbx1 in testes adversely affected sperm maturation and Cbx1 deletion increased seminiferous tubule degeneration and basal level DNA damage., We observed that Cbx1−/− MEF cells displayed reduced resolution of stalled DNA replication forks as well as decreased fork restart, indicating defective DNA synthesis. Taken together, these results suggest that loss of Cbx1 in growing cells leads to DNA replication defects and associated DNA damage that impact cell survival.


DNA Repair ◽  
10.5772/21367 ◽  
2011 ◽  
Author(s):  
Frdric Leduc ◽  
Genevive Acteau ◽  
Marie-Chantal Grgoire ◽  
Olivier Simard ◽  
Jessica Leroux ◽  
...  

2016 ◽  
Vol 54 (5) ◽  
pp. 3591-3605 ◽  
Author(s):  
Cheng Ni ◽  
Cheng Li ◽  
Yuanlin Dong ◽  
Xiangyang Guo ◽  
Yiying Zhang ◽  
...  

2019 ◽  
Vol 61 ◽  
pp. 104639 ◽  
Author(s):  
Zhenlong Kang ◽  
Na Qiao ◽  
Gaoyang Liu ◽  
Hanming Chen ◽  
Zhaoxin Tang ◽  
...  

2004 ◽  
Vol 16 (9) ◽  
pp. 2
Author(s):  
R. J. Aitken

Defective sperm function is the largest defined cause of human infertility, affecting one in twenty Australian males. Despite its prevalence, we are only just beginning to understand the underlying mechanisms. The past decade has seen two major advances in this field: (1) the discovery that Y chromosome deletions play a key role in the aetiology of non-obstructive azoospermia/oligozoospermia; and (2) recognition that oxidative stress can impact upon the functional competence of human spermatozoa through peroxidative damage to the sperm plasma membrane. Oxidative stress has also been found to disrupt the integrity of DNA in the male germ line and may represent an important mechanism by which environmental impacts on human health are mediated. Thus, paternal exposure to various toxicants (cigarette smoke, organic solvents, heavy metals) has been linked with oxidative DNA damage in spermatozoa and developmental defects, including cancer, in the F1 generation. The male germ line becomes particularly vulnerable to such factors during the post meiotic stages of differentiation. Pre-meiotic germ cells always have the option of undergoing apoptosis if DNA damage is severe. However, post meiotic germ cells have lost both the ability to mount an apoptotic response and the capacity for DNA repair. As a result, germ cells are particularly vulnerable to genotoxic agents during spermiogenesis and epididymal maturation. If the fertilizing capacity of the spermatozoa is retained following toxicant exposure, then DNA damage will be transferred to the zygote and must be repaired subsequently by the oocyte and/or early embryo. Aberrant DNA repair at this stage has the potential to create mutations that will compromise embryonic development and, ultimately, the normality of the offspring. Elucidating the causes of oxidative damage in spermatozoa should help resolve the aetiology of conditions such as male infertility, early pregnancy loss and childhood disease, including cancer.


2010 ◽  
Vol 22 (9) ◽  
pp. 98
Author(s):  
B. J. Nixon ◽  
B. Nixon ◽  
S. D. Roman

Acrylamide is a common industrial compound that has recently been identified in cooked, carbohydrate-rich foods such as potato chips, breads and cereals. Acrylamide has been found to be a reproductive toxin in rodents, eliciting male infertility and transgenerational toxicity through the male germline; thus dietary exposure to the compound may have consequences for male fertility and reproduction in humans. The aim of this project was to elucidate the mechanisms of acrylamide toxicity in male germ cells of mice. Freshly isolated early male germ cells were exposed to acrylamide and assessed for cell viability and aberrant morphology. DNA damage in these cells was also investigated using a modified version of the Comet Assay, which allows for adduct specificity. Significant increases in cell death or aberrant morphology were not observed following acrylamide exposure (1 µM, 18 hours). However, a significant increase in DNA damage (125% increase in mean tail DNA assessed by Comet) was identified; which may originate from either the metabolic conversion of acrylamide to glycidamide, leading to glycidamide adducts, or from oxidative stress. Additionally, the regulation of cytochrome P450 gene expression was measured using real time PCR and early male germ cells were found to upregulate gene expression of cytochrome P450 enzymes in response to acrylamide exposure. Collectively, these results support a genotoxic mode of action of acrylamide toxicity, in addition to potential oxidative damage in male germ cells. However, the mechanism by which acrylamide elicits toxicity in germ cells requires further investigation. Future outcomes of this research may provide insight into factors necessary for the healthy development of offspring and aid in the risk assessment of dietary acrylamide exposure in humans.


Author(s):  
J. A. Holme ◽  
C. Bjørge ◽  
M. Trbojevic ◽  
A.-K. Olsen ◽  
G. Brunborg ◽  
...  

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