Effect of coenzyme Q10 supplementation on post-vitrification mouse embryo development

Objective:To investigate the effects of coenzyme Q10(CoQ10)supplementation on post-vitrification embryo development and gross morphology.Methods:Balb/c mouse embryos were cultured in potassium simplex optimised medium(KSOM)with varying CoQ10 concentrations[0(control),20,40,and 60μM].The most effective CoQ10 concentration(40μM)was selected for subsequent post-vitrification morphology study.Embryos were randomly divided into four groups:Group A(non-vitrified without CoQ10),Group B(non-vitrified with CoQ10),Group C(vitrified without CoQ10),and Group D(vitrified with CoQ10),followed by vitrification at the 8-cell stage.Survival rates and development until the blastocyst stage were evaluated through morphological examinations using ASEBIR's system,distinguishing normal and abnormal embryos.Results:Supplementation of 40μM CoQ10 significantly increased blastocyst formation(95%)compared to the control group(92%),20μM(62%),and 60μM(56%)(P<0.001).Following vitrification,Group D exhibited a significant increase in blastocyst formation(92%)compared to Group C(82%)(P<0.05).Morphological assessments indicated superior embryo quality in Group B over Group D during the cleavage stage,morula,and blastocyst(P<0.05).Conclusions:CoQ10 supplementation exhibits promising potential to enhance preimplantation embryo development,increase blastocyst formation rates,and improve embryo quality post-vitrification.This offers a promising approach to mitigate oxidative stress on embryos,potentially improving overall assisted reproductive technology outcomes.

Effects of dietary coenzyme Q10 supplementation during gestation on the embryonic survival and reproductive performance of high‑parity sows

Background Fertility declines in high-parity sows.This study investigated whether parity-dependent declines in embryonic survival and reproductive performance could be restored by dietary coenzyme Q10(CoQ10)supplementation.Methods Two experiments were performed.In Exp.1,30 young sows that had completed their 2nd parity and 30 high-parity sows that had completed their 10^(th)parity,were fed either a control diet(CON)or a CON diet supple-mented with 1 g/kg CoQ10(+CoQ10)from mating until slaughter at day 28 of gestation.In Exp.2,a total of 314 post-weaning sows with two to nine parities were fed the CON or+CoQ10 diets from mating throughout gestation.Results In Exp.1,both young and high-parity sows had a similar number of corpora lutea,but high-parity sows had lower plasma CoQ10 concentrations,down-regulated genes involved with de novo CoQ10 synthesis in the endome-trium tissues,and greater levels of oxidative stress markers in plasma and endometrium tissues.High-parity sows had fewer total embryos and alive embryos,lower embryonic survival,and greater embryo mortality than young sows.Dietary CoQ10 supplementation increased the number of live embryos and the embryonic survival rate to levels simi-lar to those of young sows,as well as lowering the levels of oxidative stress markers.In Exp.2,sows showed a parity-dependent decline in plasma CoQ10 levels,and sows with more than four parities showed a progressive decline in the number of total births,live births,and piglets born effective.Dietary supplementation with CoQ10 increased the number of total births,live births,and born effective,and decreased the intra-litter covariation coefficients and the percentage of sows requiring farrowing assistance during parturition.Conclusions Dietary CoQ10 supplementation can improve the embryonic survival and reproductive performance of gestating sows with high parity,probably by improving the development of uterine function.

Breeding of Coenzyme Q_(10) Produced Strain by Low-Energy Ion Implantation and Optimization of Coenzyme Q_(10) Fermentation

In order to increase the production efficiency of coenzyme Q10, the original strain Agrobacterium tumefaciens ATCC 4452 was mutated by means of Nitrogen ions implantation. A mutant strain, ATX 12, with high contents of coenzyme Q10 was selected. Subsequently, the conditions such as carbohydrate concentration, nitrogen source concentration, inoculum＇s size, seed age, aeration and temperature which might affect the production of CoQ10 were investigated in detail. Under optimal conditions, the maximum concentration of the intracellular CoQ10 reached 200.3 mg/L after 80 h fed-batch fermentation, about 245% increasing in CoQ10 production after ion implantation, compared to the original strain.

Coenzyme Q10 as a therapeutic candidate for treating inherited photoreceptor degeneration

Inherited photoreceptor degeneration（IPD）：The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the eye and contains three layers of cells：the outer nuclear layer（ONL）containing the cell bodies and nuclei of the light-sensitive rod and cone photoreceptorswhose photopigment-containing outer segments form the photoreceptor layer; the inner nuclear layer （INL） containing bipolar, horizontal and amacrine cells; and the ganglion cell layer （GCL） from which the optic nerve arises. There are two layers of synaptic connections between these three layers： the photoreceptors synapse with second order neurons, mainly bi- polar cells, in the outer plexiform layer （OPL）, while in turn the bipolar cells form connections in the inner plexiform layer （IPL） with ganglion cells. The retinal pigment epithelium （RPE） lies directly behind the photoreceptor layer, is heavily pigmented to reduce scattering of light, and is essential for the nourishment, maintenance and metabolism of photoreceptors.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

AIMTo determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration.

Higher levels of the lipophilic antioxidants coenzyme Q_(10) and vitamin E in long-lived termite queens than in short-lived workers

Termite queens and kings live longer than nonreproductive workers.Several molecular mechanisms contributing to their long lifespan have been investigated;however,the underlying biochemical explanation remains unclear.Coenzyme Q(CoQ),a component of the mitochondrial electron transport chain,plays an essential role in the lipophilic antioxidant defense system.Its beneficial effects on health and longevity have been well studied in several organisms.Herein,we demonstrated that long-lived termite queens have significantly higher levels of the lipophilic antioxidant CoQ_(10) than workers.Liquid chromatography analysis revealed that the levels of the reduced form of CoQ_(10) were 4 fold higher in the queen's body than in the worker's body.In addition,queens showed 7 fold higher levels of vitamin E,which plays a role in antilipid peroxidation along with CoQ,than workers.Furthermore,the oral administration of CoQ_(10) to termites increased the CoQ_(10) redox state in the body and their survival rate under oxidative stress.These findings suggest that CoQ_(10) acts as an efficient lipophilic antioxidant along with vitamin E in long-lived termite queens.This study provides essential biochemical and evolutionary insights into the relationship between CoQ_(10) concentrations and termite lifespan extension.

Delivery of coenzyme Q10 loaded micelle targets mitochondrial ROS and enhances efficiency of mesenchymal stem cell therapy in intervertebral disc degeneration

Stem cell transplantation has been proved a promising therapeutic instrument in intervertebral disc degeneration(IVDD).However,the elevation of oxidative stress in the degenerated region impairs the efficiency of mesenchymal stem cells(BMSCs)transplantation treatment via exaggeration of mitochondrial ROS and promotion of BMSCs apoptosis.Herein,we applied an emulsion-confined assembly method to encapsulate Coenzyme Q10(Co-Q10),a promising hydrophobic antioxidant which targets mitochondria ROS,into the lecithin micelles,which renders the insoluble Co-Q10 dispersible in water as stable colloids.These micelles are injectable,which displayed efficient ability to facilitate Co-Q10 to get into BMSCs in vitro,and exhibited prolonged release of Co-Q10 in intervertebral disc tissue of animal models.Compared to mere use of Co-Q10,the Co-Q10 loaded micelle possessed better bioactivities,which elevated the viability,restored mitochondrial structure as well as function,and enhanced production of ECM components in rat BMSCs.Moreover,it is demonstrated that the injection of this micelle with BMSCs retained disc height and alleviated IVDD in a rat needle puncture model.Therefore,these Co-Q10 loaded micelles play a protective role in cell survival and differentiation through antagonizing mitochondrial ROS,and might be a potential therapeutic agent for IVDD.

Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo

CoQ is an essential electron cartier in the mitochondrial respiratory chain of both eukaryotes and prokaryotes. It consists of a benzoquinone head group and a hydrophobic polyisoprenoid tail. The genes （COQ1-9） involved in CoQ biosynthesis have been characterized in yeast. In this study, we generated and molecularly characterized a mutant allele of a novel Drosophila gene, sbo, which encodes a protein that is predicted to catalyze the prenylation of p-hydroxybenzoate with the isoprenoid chain during the process of CoQ synthesis. Expression of sbo in yeast rescues the lethality of ACOQ2 mutant cells, indicating that sbo is a functional homolog of COQ2. HPLC results show that the levels of CoQ9 and COQlo were significantly reduced in sbo heterozygous adult flies. Furthermore, the mean lifespans of males and females heterozygous for sbo are extended by 12.5% and 30.8%, respectively. Homozygous sbo animals exhibit reduced activities of the insulin/insulin-like growth factor signaling （IIS） pathway. Taken together, we conclude that sbo is an essential gene for Drosophila development, mutation of which leads to an extension of lifespan most likely by altering endogenous CoQ biosynthesis.

How plants synthesize coenzyme Q

Coenzyme Q(CoQ)is a conserved redox-active lipid that has a wide distribution across the domains of life.CoQ plays a key role in the oxidative electron transfer chain and serves as a crucial antioxidant in cellular membranes.Our understanding of CoQ biosynthesis in eukaryotes has come mostly from studies of yeast.Recently,significant advances have been made in understanding CoQ biosynthesis in plants.Unique mitochondrial flavin-dependent monooxygenase and benzenoid ring precursor biosynthetic pathways have been discovered,providing new insights into the diversity of CoQ biosynthetic pathways and the evolution of phototrophic eukaryotes.We summarize research progress on CoQ biosynthesis and regulation in plants and recent efforts to increase the CoQ content in plant foods.

Progression of intervention-focused research for Gulf War illness

The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide(PB),smoke from burning oil wells,and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops.The cluster of chronic symptoms,now referred to as Gulf War Illness(GWI),has been studied by many researchers over the past two decades.Although over$500 million has been spent on GWI research,to date,no cures or condition-specific treatments have been discovered,and the exact pathophysiology remains elusive.Using the 2007 National Institute of Health(NIH)Roadmap for Medical Research model as a reference framework,we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research.All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms.After reviewing the published and ongoing registered clinical trials for cognitivebehavioral therapy,exercise therapy,acupuncture,coenzyme Q10(CoQ10),mifepristone,and carnosine in GWI patients,we identified only four treatments(cognitive-behavioral therapy,exercise therapy,CoQ10,and mifepristone)that have progressed beyond a phase II trial.We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model.Establishment of a standard case definition,prioritized GWI research funding for the characterization of the pathophysiology of the condition,and rapid replication and adaptation of early phase,single site clinical trials could substantially advance research progress and treatment discovery for this condition.