scholarly journals Genetic Association in the Maintenance of the Mitochondrial Microenvironment and Sperm Capacity

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Hwang I. S. Thomas ◽  
Ying-Shiuan Chen ◽  
Ching-Han Hung ◽  
Dilip Bhargava Sreerangaraja Urs ◽  
Tien-Ling Liao ◽  
...  

Sperm motility is one of the major determinants of male fertility. Since sperm need a great deal of energy to support their fast movement by active metabolism, they are thus extremely vulnerable to oxidative damage by the reactive oxygen species (ROS) and other free radicals generated as byproducts in the electron transport chain. The present study is aimed at understanding the impact of a mitochondrial oxidizing/reducing microenvironment in the etiopathology of male infertility. We detected the mitochondrial DNA (mtDNA) 4,977 bp deletion in human sperm. We examined the gene mutation of ATP synthase 6 (ATPase6 m.T8993G) in ATP generation, the gene polymorphisms of uncoupling protein 2 (UCP2, G-866A) in the uncoupling of oxidative phosphorylation, the role of genes such as manganese superoxide dismutase (MnSOD, C47T) and catalase (CAT, C-262T) in the scavenging system in neutralizing reactive oxygen species, and the role of human 8-oxoguanine DNA glycosylase (hOGG1, C1245G) in 8-hydroxy-2 ′ -deoxyguanosine (8-OHdG) repair. We found that the sperm with higher motility were found to have a higher mitochondrial membrane potential and mitochondrial bioenergetics. The genotype frequencies of UCP2 G-866A, MnSOD C47T, and CAT C-262T were found to be significantly different among the fertile subjects, the infertile subjects with more than 50% motility, and the infertile subjects with less than 50% motility. A higher prevalence of the mtDNA 4,977 bp deletion was found in the subjects with impaired sperm motility and fertility. Furthermore, we found that there were significant differences between the occurrences of the mtDNA 4,977 bp deletion and MnSOD (C47T) and hOGG1 (C1245G). In conclusion, the maintenance of the mitochondrial redox microenvironment and genome integrity is an important issue in sperm motility and fertility.

Author(s):  
Durg V. Rai ◽  
Harcharan Singh Ranu

Ovarian hormone deficiency increases the generation of reactive oxygen species. Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage to cells. Cells have a number of defense mechanisms to protect themselves from the toxicity of ROS. There is increasing evidence of the role of free radicals in bone resorption and bone loss. Ovariectomised female wistar rats had been used as the animal model for the study of osteoporosis. Even though, there are studies portraying the role of free radicals in bone loss, the defense mechanism adapted by bone in ovariectomised animals remains obscure. So, the impact of ovariectomy on the bone antioxidant system in rats was investigated. Twenty female wistar rats were taken and divided into two groups: ovariectomised and control. It had been found that a significant (p<0.001) decrease in the activity of various enzymes like CAT (catalase), SOD (superoxide dismutase) (p<0.001), GST (glutathione-s-transferase). However, an increase in the malondialdehyde levels was found to be 30% in the ovariectomised rats as compared to the controls. Thus the study elucidates the oxidative stress in bone under ovariectomy.


2006 ◽  
Vol 100 (2) ◽  
pp. 739-743 ◽  
Author(s):  
Frank M. Faraci

Reactive oxygen species have multiple effects on vascular cells. Defining the sources and the impact of the various reactive oxygen species within the vessel wall has emerged as a major area of study in vascular biology. This review will focus on recent findings related to effects of reactive oxygen species on cerebral vascular tone. Effects of superoxide radical, hydrogen peroxide, and the reactive nitrogen species peroxynitrite are summarized. Although higher concentrations may be important for cerebral vascular biology in disease, relatively low concentrations of reactive oxygen species may function as signaling molecules involved with normal regulation of cerebral vascular tone. The mechanisms by which reactive oxygen species affect vascular tone may be quite complex, and our understanding of these processes is increasing. Additionally, the role of reactive oxygen species as mediators of endothelium-dependent relaxation is addressed. Finally, the consequences of the molecular interactions of superoxide with nitric oxide and arachidonic acid are discussed.


Andrologia ◽  
2010 ◽  
Vol 42 (3) ◽  
pp. 206-210 ◽  
Author(s):  
S. S. Du Plessis ◽  
D. A. McAllister ◽  
A. Luu ◽  
J. Savia ◽  
A. Agarwal ◽  
...  

2009 ◽  
Vol 203 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Simon C Lee ◽  
Christine A Robson-Doucette ◽  
Michael B Wheeler

Currently, the physiological function of uncoupling protein-2 (UCP2) in pancreatic islets and its role in the development of diabetes is a matter of great debate. To further investigate the impact of UCP2 on diabetes development, we used streptozotocin (STZ) to experimentally generate diabetes in both wild-type (WT) and UCP2-knockout (UCP2KO) mice. While multiple low-dose STZ injections led to hyperglycemia development over a 14-day period in both WT and UCP2KO mice, we found the development of hyperglycemia to be significantly less severe in the UCP2KO mice. Measurement of insulin and glucagon secretion (in vitro), as well as their plasma concentrations (in vivo), indicated that UCP2-deficiency showed enhanced insulin secretion but impaired α-cell function. Glucagon secretion was attenuated, despite reduced insulin secretion after exposure to STZ, which together contributed to less severe hyperglycemia development in UCP2KO mice. Further experimentation revealed that UCP2-deficient α- and β-cells had chronically higher cellular reactive oxygen species (ROS) levels than the WT prior to STZ application, which correlated with increased basal β- and α-cell mass. Overall, we suggest that increased chronic ROS signaling as a result of UCP2-deficiency contributes to enhanced β-cell function and impairment of α-cell function, leading to an attenuation of STZ-induced hyperglycemia development.


2001 ◽  
Vol 281 (6) ◽  
pp. H2568-H2574 ◽  
Author(s):  
Milind V. Gurjar ◽  
Jason Deleon ◽  
Ram V. Sharma ◽  
Ramesh C. Bhalla

We have recently demonstrated that interleukin-1β (IL-1β) stimulates matrix metalloproteinase-9 (MMP-9) induction. In this study we have investigated the roles of superoxide and extracellular signal-regulated kinase (ERK) activation in MMP-9 induction following exposure to IL-1β. IL-1β stimulated biphasic ERK activation in vascular smooth muscle (VSM) cells, a transient activation that reached a maximum at 15 min and declined to baseline levels within 1 h, and a second phase of sustained ERK activation lasting up to 8 h. To determine the role of ERK in IL-1β-stimulated MMP-9 induction, we treated cells with the specific ERK pathway inhibitor PD-98059 at different time intervals after IL-1β stimulation. Addition of PD-98059 up to 4 h after IL-1β stimulation significantly inhibited MMP-9 induction, suggesting a role for sustained ERK activation in MMP-9 induction. IL-1β treatment stimulated superoxide production in VSM cells that was inhibited by pretreatment of cells with the superoxide scavenger N-acetyl-l-cysteine (NAC) and also by overexpression of the human manganese superoxide dismutase (MnSOD) gene. Treatment of VSM cells with NAC selectively inhibited the sustained phase of ERK activation without influencing the transient phase, suggesting a role for reactive oxygen species in sustained ERK activation. In addition, both NAC treatment and MnSOD overexpression significantly inhibited IL-1β-stimulated MMP-9 induction ( P < 0.05). The results demonstrate that IL-1β-dependent MMP-9 induction is mediated by superoxide-stimulated ERK activation.


Andrologia ◽  
2011 ◽  
Vol 44 ◽  
pp. 696-703 ◽  
Author(s):  
T.-Y. Shi ◽  
G. Chen ◽  
X. Huang ◽  
Y. Yuan ◽  
X. Wu ◽  
...  

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