scholarly journals Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 933 ◽  
Author(s):  
James N. Cobley

The consensus that assisted reproduction technologies (ART), like in vitro fertilization, to induce oxidative stress (i.e., the known) belies how oocyte/zygote mitochondria—a major presumptive oxidative stressor—produce reactive oxygen species (ROS) with ART being unknown. Unravelling how oocyte/zygote mitochondria produce ROS is important for disambiguating the molecular basis of ART-induced oxidative stress and, therefore, to rationally target it (e.g., using site-specific mitochondria-targeted antioxidants). I review the known mechanisms of ROS production in somatic mitochondria to critique how oocyte/zygote mitochondria may produce ROS (i.e., the unknown). Several plausible site- and mode-defined mitochondrial ROS production mechanisms in ART are proposed. For example, complex I catalyzed reverse electron transfer-mediated ROS production is conceivable when oocytes are initially extracted due to at least a 10% increase in molecular dioxygen exposure (i.e., the intriguing). To address the term oxidative stress being used without recourse to the underlying chemistry, I use the species-specific spectrum of biologically feasible reactions to define plausible oxidative stress mechanisms in ART. Intriguingly, mitochondrial ROS-derived redox signals could regulate embryonic development (i.e., their production could be beneficial). Their potential beneficial role raises the clinical challenge of attenuating oxidative damage while simultaneously preserving redox signaling. This discourse sets the stage to unravel how mitochondria produce ROS in ART, and their biological roles from oxidative damage to redox signaling.

2010 ◽  
Vol 108 (4) ◽  
pp. 780-787 ◽  
Author(s):  
Kent Sahlin ◽  
Irina G. Shabalina ◽  
C. Mikael Mattsson ◽  
Linda Bakkman ◽  
Maria Fernström ◽  
...  

Exercise-induced oxidative stress is important for the muscular adaptation to training but may also cause muscle damage. We hypothesized that prolonged exercise would increase mitochondrial production of reactive oxygen species (ROS) measured in vitro and that this correlates with oxidative damage. Eight male athletes (24–32 yr) performed ultraendurance exercise (kayaking/running/cycling) with an average work intensity of 55% V̇o2peak for 24 h. Muscle biopsies were taken from vastus lateralis before exercise, immediately after exercise, and after 28 h of recovery. The production of H2O2 was measured fluorometrically in isolated mitochondria with the Amplex red and peroxidase system. Succinate-supported mitochondrial H2O2 production was significantly increased after exercise (73% higher, P = 0.025) but restored to the initial level at recovery. Plasma level of free fatty acids (FFA) increased fourfold and exceeded 1.2 mmol/l during the last 6 h of exercise. Plasma FFA at the end of exercise was significantly correlated to mitochondrial ROS production ( r = 0.74, P < 0.05). Mitochondrial content of 4-hydroxy-nonenal-adducts (a marker of oxidative damage) was increased only after recovery and was not correlated with mitochondrial ROS production. Total thiol group level and glutathione peroxidase activity were elevated after recovery. In conclusion, ultraendurance exercise increases ROS production in isolated mitochondria, but this is reversed after 28 h recovery. Mitochondrial ROS production was not correlated with oxidative damage of mitochondrial proteins, which was increased at recovery but not immediately after exercise.


Author(s):  
Laura Gambera ◽  
Anita Stendardi ◽  
Camilla Ghelardi ◽  
Benedetta Fineschi ◽  
Rosamaria Aini

Objective: The aim of this non controlled trial was to assess whether a therapy with an antioxidant supplement may improve spermatozoa quality in terms of number, motility, morphology and a higher number of successful conceptions in patients with oligoasthenoteratozoospermia undergoing cycles of medically assisted reproduction by intracytoplasmic sperm injection (ICSI). Materials and methods: 32 patients registered at A.G.I. Medica (Siena) medically assisted reproduction centre affected by fertility problems associated with oligoasthenoteratozoospermia were included in the study. Semen analysis were evaluated according to World Health Organization 2010, before and after treatment. Moreover, we used colorimetric tests to assess oxidative stress. After evaluating oocyte fertilisation rate and the quality of embryos obtained, data were statistically analysed. Result: Microscopy examination after the therapy, showed a general improvement in sperm parameters (number of sperms, progressive motility, viability and normal morphology) in both baseline and capacitated; also the levels of oxidative stress was notably lower after the treatment. Morever we evaluated the outcome of the IVF treatment, the percentage of fertilization and the number of embryos obtained, all the parameters was significantly higher in the N1 group. Conclusions: The outcomes of this trial seem to suggest that the administration of our food supplement improve semen parameters and that the evaluation of oxidative stress levels may become a diagnostic tool to assess male infertility in patients undergoing ART cycle.


1997 ◽  
Vol 16 (2) ◽  
pp. 279-288 ◽  
Author(s):  
Robert H. Blank

In vitro fertilization (IVF) and other assisted reproduction technologies (ARTs) have become widely accepted as therapy for a wide array of fertility problems and accompanied by the rapid expansion of clinics that provide a full range of ARTs. Although these technologies undoubtedly offer benefits for some individuals, they raise important questions over reproductive rights to safe and effective treatment as well as access. This article analyzes current data concerning the safety, effectiveness, and cost of IVF. It concludes that IVF and related techniques have been transformed too rapidly and easily from experimental to therapy status, despite evidence that suggests considerable caution is warranted. Unfortunately, the widespread diffusion of IVF has preceded rather than followed firm evidence of its value in extending the reproductive rights of women and couples. Resources might better be directed toward prevention of fertility problems and discovering the causes of infertility.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
I Koutagiar ◽  
C Vlachopoulos ◽  
D Terentes-Printzios ◽  
I Kosteria ◽  
S Sakka ◽  
...  

Abstract Background Since the introduction of Assisted Reproduction Technologies (ART) in clinical practice several studies have addressed concerns regarding the long-term health of the offspring and have revealed indications of an adverse cardiovascular/cardiometabolic outcome. Proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipoprotein (a) (Lp[a]) levels have been associated with cardiovascular risk. Purpose To investigate PCSK9 and Lp(a) levels of children born after ART compared with naturally conceived (NC) controls. Methods In this case-control study, 73 sex- and age-matched children (mean age 98±35 months) of ART (intracytoplasmic sperm injection [ICSI]: n=33, classic in vitro fertilization [IVF]: n=40) and 73 NC children were assessed. Blood lipid profile, including PCSK9 and Lp(a) levels, was measured. Children were grouped according to age (<8 years, 8–10 years, ≥10 years). Results In the univariate model of the overall population, circulating PCSK9 levels were related to total cholesterol (r=0.186, P=0.025), LDL-C (r=0.180, P=0.029) and SBP (r=0.199, P=0.021). Similarly, circulating Lp(a) levels were related to age (r=0.269, P=0.001), apoB (r=0.214, P=0.01), birth weight (r=−0.183, P=0.037), height (r=0.263, P=0.001), waist-to-hip ratio (r=−0.350, P<0.001), HOMA-IR (r=0.319, P<0.001), insulin (r=0.316, P<0.001), and hsCRP (ρ=0.241, P=0.018). No significant differences were observed regarding lipid biomarkers between ART and NC children. (p=0.515 for PCSK9 and p=0.277 for Lp(a) values). It is noteworthy that a significant interaction was found between age groups and conception method (P<0.001) showing that PCSK9 levels increase with age in ART children, while they decline with age in NC offspring (Figure 1). IVF children showed higher levels of adjusted mean Lp(a) than ICSI (13.5 vs. 6.8 mg/dl, P=0.010) and NC children (12.3 vs. 8.3 mg/dl, P=0.048). Mean LogPCSK9 concentrations with the st Conclusions PCSK9 and Lp(a) levels did not differ between ART and NC children. Nonetheless, PCSK9 levels increase with age in ART children indicating a gradual deterioration of lipidemic profile that could lead to increased cardiovascular risk. Moreover, our results imply that ART method may be of importance given that classic IVF is associated with higher levels of Lp(a). The impact of the method of conception on PCSK9 and Lp(a) values should be validated in larger patient series.


Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1025
Author(s):  
Roberto Gualtieri ◽  
Guruprasad Kalthur ◽  
Vincenza Barbato ◽  
Salvatore Longobardi ◽  
Francesca Di Rella ◽  
...  

Reactive oxygen species (ROS) generated at low levels during mitochondrial respiration have key roles in several signaling pathways. Oxidative stress (OS) arises when the generation of ROS exceeds the cell’s antioxidant scavenging ability and leads to cell damage. Physiological ROS production in spermatozoa regulates essential functional characteristics such as motility, capacitation, acrosome reaction, hyperactivation, and sperm-oocyte fusion. OS can have detrimental effects on sperm function through lipid peroxidation, protein damage, and DNA strand breakage, which can eventually affect the fertility of an individual. Substantial evidence in the literature indicates that spermatozoa experiencing OS during in vitro manipulation procedures in human- and animal-assisted reproduction are increasingly associated with iatrogenic ROS production and eventual impairment of sperm function. Although a direct association between sperm OS and human assisted reproductive techniques (ART) outcomes after in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) is still a matter of debate, studies in animal models provide enough evidence on the adverse effects of sperm OS in vitro and defective fertilization and embryo development. This review summarized the literature on sperm OS in vitro, its effects on functional ability and embryo development, and the approaches that have been proposed to reduce iatrogenic sperm damage and altered embryonic development.


2018 ◽  
Author(s):  
Maja Djundeva ◽  
Ivett Szalma

This paper contributes to the literature on social acceptance of artificial insemination and in-vitro fertilization, the two most prominent examples of Assisted Reproduction Technologies (ART) in Europe and direct attention to several previously under-researched aspects. The empirical base of this study is the fourth round of the European Values Study (EVS), conducted in 2008-2010 in 43 countries. Using multilevel fixed-effects linear regressions, we examine the impact of several individual and country-level characteristics on the agreement level with the statement that artificial insemination or in-vitro fertilization can always be justified, never be justified or something in between. According to our findings there are strong relationships between attitudes towards ART and socio-demographic variables, as well as religiousness and individual attitudes such as traditional family formation practices, "justification of homosexuality", (non-)preference for homosexual neighbours and acceptance of adoption by homosexual couples. As for the country level variables we found significant effect in case of those variables which are related to social changes within the concept Second Demographic Transitions such as mean age at first birth and secularization but GDP did not have any significant effects.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fujiao Nie ◽  
Jiazhao Yan ◽  
Yanjun Ling ◽  
Zhengrong Liu ◽  
Chaojun Fu ◽  
...  

Abstract Background Diabetic retinopathy (DR) has become a worldwide concern because of the rising prevalence rate of diabetes mellitus (DM). Despite much energy has been committed to DR research, it remains a difficulty for diabetic patients all over the world. Since apoptosis of retinal microvascular pericytes (RMPs) is the early characteristic of DR, this study aimed to reveal the mechanism of Shuangdan Mingmu (SDMM) capsule, a Chinese patent medicine, on oxidative stress-induced apoptosis of pericytes implicated with poly (ADP-ribose) polymerase (PARP) / glyceraldehyde 3-phosphate dehydrogenase (GAPDH) pathway. Methods Network pharmacology approach was performed to predict biofunction of components of SDMM capsule dissolved in plasma on DR. Both PARP1 and GAPDH were found involved in the hub network of protein-protein interaction (PPI) of potential targets and were found to take part in many bioprocesses, including responding to the regulation of reactive oxygen species (ROS) metabolic process, apoptotic signaling pathway, and response to oxygen levels through enrichment analysis. Therefore, in vitro research was carried out to validate the prediction. Human RMPs cultured with media containing 0.5 mM hydrogen oxide (H2O2) for 4 h was performed as an oxidative-damage model. Different concentrations of SDMM capsule, PARP1 inhibitor, PARP1 activation, and GAPDH inhibitor were used to intervene the oxidative-damage model with N-Acetyl-L-cysteine (NAC) as a contrast. Flow cytometry was performed to determine the apoptosis rate of cells and the expression of ROS. Cell counting kit 8 (CCK8) was used to determine the activity of pericytes. Moreover, nitric oxide (NO) concentration of cells supernatant and expression of endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD), B cell lymphoma 2 (BCL2), vascular endothelial growth factor (VEGF), endothelin 1 (ET1), PARP1, and GAPDH were tested through RT-qPCR, western blot (WB), or immunocytochemistry (ICC). Results Overproduction of ROS, high apoptotic rate, and attenuated activity of pericytes were observed after cells were incubated with media containing 0.5 mM H2O2. Moreover, downregulation of SOD, NO, BCL2, and GAPDH, and upregulation of VEGFA, ET1, and PARP1 were discovered after cells were exposed to 0.5 mM H2O2 in this study, which could be improved by PARP1 inhibitor and SDMM capsule in a dose-dependent way, whereas worsened by PARP1 activation and GAPDH inhibitor. Conclusions SDMM capsule may attenuate oxidative stress-induced apoptosis of pericytes through downregulating PARP expression and upregulating GAPDH expression.


2021 ◽  
Vol 22 (9) ◽  
pp. 4368
Author(s):  
Heriberto Rodriguez-Martinez ◽  
Emilio A. Martinez ◽  
Juan J. Calvete ◽  
Fernando J. Peña Vega ◽  
Jordi Roca

Seminal plasma (SP), the non-cellular component of semen, is a heterogeneous composite fluid built by secretions of the testis, the epididymis and the accessory sexual glands. Its composition, despite species-specific anatomical peculiarities, consistently contains inorganic ions, specific hormones, proteins and peptides, including cytokines and enzymes, cholesterol, DNA and RNA—the latter often protected within epididymis- or prostate-derived extracellular vesicles. It is beyond question that the SP participates in diverse aspects of sperm function pre-fertilization events. The SP also interacts with the various compartments of the tubular genital tract, triggering changes in gene function that prepares for an eventual successful pregnancy; thus, it ultimately modulates fertility. Despite these concepts, it is imperative to remember that SP-free spermatozoa (epididymal or washed ejaculated) are still fertile, so this review shall focus on the differences between the in vivo roles of the SP following semen deposition in the female and those regarding additions of SP on spermatozoa handled for artificial reproduction, including cryopreservation, from artificial insemination to in vitro fertilization. This review attempts, including our own results on model animal species, to critically summarize the current knowledge of the reproductive roles played by SP components, particularly in our own species, which is increasingly affected by infertility. The ultimate goal is to reconcile the delicate balance between the SP molecular concentration and their concerted effects after temporal exposure in vivo. We aim to appraise the functions of the SP components, their relevance as diagnostic biomarkers and their value as eventual additives to refine reproductive strategies, including biotechnologies, in livestock models and humans.


2017 ◽  
Vol 44 (4) ◽  
pp. 288-293 ◽  
Author(s):  
Shiho Yamadera ◽  
Yuya Nakamura ◽  
Masahiro Inagaki ◽  
Isao Ohsawa ◽  
Hiromichi Gotoh ◽  
...  

Aim: To examine the effects of vitamin E-coated dialyzer on oxidative stress in vitro. Methods: A dialyzer with a synthetic polymer membrane (APS-11SA) and vitamin E-coated dialyzer (VPS-11SA) were connected to a blood tubing line, and U937 cells were circulated in the device. The circulating fluid was collected at 1, 2, 5, 10, 25, and 50 cycles, which are estimated numbers of passes through the dialyzer. Intracellular reactive oxygen species (ROS) production, malondialdehyde (MDA), and Cu/Zn-superoxide dismutase (SOD) were quantified. Results: Intracellular ROS production was increased in the first cycle by APS-11SA and was decreased throughout the experiment by VPS-11SA. Intracellular ROS production in the VPS-11SA device was lower, and MDA levels were decreased. MDA levels were lower during VPS-11SA processing than during APS-11SA processing. Cu/Zn-SOD levels remained unchanged. Conclusion: Our results highlight anti-oxidative-stress effects of a vitamin E-coated dialyzer.


2020 ◽  
Vol 55 (9) ◽  
pp. 1103-1114
Author(s):  
Pei‐Pei Zhang ◽  
Jing‐Jing Wang ◽  
Chong‐Yang Li ◽  
Hai‐sheng Hao ◽  
Hao‐Yu Wang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document