OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The impact of oxidative stress on reproduction: a focus on gametogenesis and fertilizationAitken, R John; Bromfield, Elizabeth G; Gibb, Zamira
doi: 10.1530/rep-22-0126pmid: 35929832
In briefMany aspects of the reproductive process are impacted by oxidative stress. This article summarizes the chemical nature of reactive oxygen species and their role in both the physiological regulation of reproductive processes and the pathophysiology of infertility.AbstractThis article lays out the fundamental principles of oxidative stress. It describes the nature of reactive oxygen species (ROS), the way in which these potentially toxic metabolites interact with cells and how they impact both cellular function and genetic integrity. The mechanisms by which ROS generation is enhanced to the point that the cells’ antioxidant defence mechanisms are overwhelmed are also reviewed taking examples from both the male and female reproductive system, with a focus on gametogenesis and fertilization. The important role of external factors in exacerbating oxidative stress and impairing reproductive competence is also examined in terms of their ability to disrupt the physiological redox regulation of reproductive processes. Developing diagnostic and therapeutic strategies to cope with oxidative stress within the reproductive system will depend on the development of a deeper understanding of the nature, source, magnitude, and location of such stress in order to fashion personalized treatments that meet a given patient’s clinical needs.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Reactive oxygen species in the mammalian pre-implantation embryoDeluao, Joshua C; Winstanley, Yasmyn; Robker, Rebecca L; Pacella-Ince, Leanne; Gonzalez, Macarena B; McPherson, Nicole O
doi: 10.1530/rep-22-0121pmid: 36111646
In briefReactive oxygen species are generated throughout the pre-implantation period and are necessary for normal embryo formation. However, at pathological levels, they result in reduced embryo viability which can be mediated through factors delivered by sperm and eggs at conception or from the external environment.AbstractReactive oxygen species (ROS) occur naturally in pre-implantation embryos as a by-product of ATP generation through oxidative phosphorylation and enzymes such as NADPH oxidase and xanthine oxidase. Biological concentrations of ROS are required for crucial embryonic events such as pronuclear formation, first cleavage and cell proliferation. However, high concentrations of ROS are detrimental to embryo development, resulting in embryo arrest, increased DNA damage and modification of gene expression leading to aberrant fetal growth and health. In vivo embryos are protected against oxidative stress by oxygen scavengers present in follicular and oviductal fluids, while in vitro, embryos rely on their own antioxidant defence mechanisms to protect against oxidative damage, including superoxide dismutase, catalase, glutathione and glutamylcysteine synthestase. Pre-implantation embryonic ROS originate from eggs, sperm and embryos themselves or from the external environment (i.e. in vitro culture system, obesity and ageing). This review examines the biological and pathological roles of ROS in the pre-implantation embryo, maternal and paternal origins of embryonic ROS, and from a clinical perspective, we comment on the growing interest in combating increased oxidative damage in the pre-implantation embryo through the addition of antioxidants.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Sperm telomeres, oxidative stress, and infertilityMoazamian, Aron; Gharagozloo, Parviz; Aitken, Robert J; Drevet, Joël R
doi: 10.1530/rep-22-0189pmid: 35938805
In briefOxidative stress is recognized as an underlying driving factor of both telomere dysfunction and human subfertility/infertility. This review briefly reassesses telomere integrity as a fertility biomarker before proposing a novel, mechanistic rationale for the role of oxidative stress in the seemingly paradoxical lengthening of sperm telomeres with aging.AbstractThe maintenance of redox balance in the male reproductive tract is critical to sperm health and function. Physiological levels of reactive oxygen species (ROS) promote sperm capacitation, while excess ROS exposure, or depleted antioxidant defenses, yields a state of oxidative stress which disrupts their fertilizing capacity and DNA structural integrity. The guanine moiety is the most readily oxidized of the four DNA bases and gets converted to the mutagenic lesion 8-hydroxy-deoxyguanosine (8-OHdG). Numerous studies have also confirmed oxidative stress as a driving factor behind accelerated telomere shortening and dysfunction. Although a clear consensus has not been reached, clinical studies also appear to associate telomere integrity with fertility outcomes in the assisted reproductive technology setting. Intriguingly, while sperm cellular and molecular characteristics make them more susceptible to oxidative insult than any other cell type, they are also the only cell type in which telomere lengthening accompanies aging. This article focuses on the oxidative stress response pathways to propose a mechanism for the explanation of this apparent paradox.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress and in vitro ageing of the post-ovulatory oocyte: an update on recent advances in the fieldMartin, Jacinta H; Nixon, Brett; Cafe, Shenae L; Aitken, R John; Bromfield, Elizabeth G; Lord, Tessa
doi: 10.1530/rep-22-0206pmid: 36190194
In briefPost-ovulatory ageing of oocytes leads to poor oocyte and embryo quality as well as abnormalities in offspring. This review provides an update on the contributions of oxidative stress to this process and discusses the current literature surrounding the use of antioxidant media to delay post-ovulatory oocyte ageing.AbstractFollowing ovulation, the metaphase II stage oocyte has a limited functional lifespan before succumbing to a process known as post-ovulatory oocyte ageing. This progressive demise occurs both in vivo and in vitro and is accompanied by a deterioration in oocyte quality, leading to a well-defined sequelae of reduced fertilisation rates, poor embryo quality, post-implantation errors, and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been characterised, less is known regarding the molecular mechanisms that drive this process. This review presents an update on the established relationships between the biochemical changes exhibited by the ageing oocyte and the myriad of symptoms associated with the ageing phenotype. In doing so, we consider the molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We highlight the mounting evidence that oxidative stress acts as an initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to disrupt mitochondrial function and directly damage multiple intracellular components of the oocyte such as lipids, proteins, and DNA. Finally, this review addresses emerging strategies for delaying post-ovulatory oocyte ageing with emphasis placed on the promise afforded by the use of selected antioxidants to guide the development of media tailored for the preservation of oocyte integrity during in vitro fertilisation procedures.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress and in vitro ageing of the post-ovulatory oocyte: an update on recent advances in the fieldMartin, Jacinta H; Nixon, Brett; Cafe, Shenae L; Aitken, R John; Bromfield, Elizabeth G; Lord, Tessa
doi: 10.1530/rep-22-0206pmid: 36190194
In briefPost-ovulatory ageing of oocytes leads to poor oocyte and embryo quality as well as abnormalities in offspring. This review provides an update on the contributions of oxidative stress to this process and discusses the current literature surrounding the use of antioxidant media to delay post-ovulatory oocyte ageing.AbstractFollowing ovulation, the metaphase II stage oocyte has a limited functional lifespan before succumbing to a process known as post-ovulatory oocyte ageing. This progressive demise occurs both in vivo and in vitro and is accompanied by a deterioration in oocyte quality, leading to a well-defined sequelae of reduced fertilisation rates, poor embryo quality, post-implantation errors, and abnormalities in the offspring. Although the physiological consequences of post-ovulatory oocyte ageing have largely been characterised, less is known regarding the molecular mechanisms that drive this process. This review presents an update on the established relationships between the biochemical changes exhibited by the ageing oocyte and the myriad of symptoms associated with the ageing phenotype. In doing so, we consider the molecular events that are potentially involved in orchestrating post-ovulatory ageing with a particular focus on the role of oxidative stress. We highlight the mounting evidence that oxidative stress acts as an initiator for a cascade of events that create the aged oocyte phenotype. Specifically, oxidative stress has the capacity to disrupt mitochondrial function and directly damage multiple intracellular components of the oocyte such as lipids, proteins, and DNA. Finally, this review addresses emerging strategies for delaying post-ovulatory oocyte ageing with emphasis placed on the promise afforded by the use of selected antioxidants to guide the development of media tailored for the preservation of oocyte integrity during in vitro fertilisation procedures.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The protection of mammalian spermatozoa against oxidative stressO’Flaherty, Cristian; Scarlata, Eleonora
doi: 10.1530/rep-22-0200pmid: 37021966
In briefThis review focuses on the enzymatic antioxidant mechanisms to fight oxidative stress by spermatozoa, highlighting the differences among mammalian species. We discuss recent evidence about players that promote and fight oxidative stress and the need for novel strategies to diagnose and treat cases of male infertility associated with oxidative damage of the spermatozoon.AbstractThe spermatozoon is very sensitive to high reactive oxygen species (ROS) levels due to its limited antioxidant system. A consortium of antioxidant enzymes, including superoxide dismutase (SOD), glutathione peroxidases (GPXs), peroxiredoxins (PRDXs), thioredoxins, and glutathione-S-transferases, is necessary to produce healthy spermatozoa and to maintain sperm quality to ensure motility, capacitation, and DNA integrity. A delicate balance between ROS production and antioxidant enzymes is needed to ensure ROS-dependent sperm capacitation. GPX4 is an essential component of the mitochondrial sheath in mammalian spermatozoa, and GPX5 is a crucial antioxidant defence in the mouse epididymis to protect the sperm genome during the maturation of the spermatozoon. The mitochondrial superoxide (O2·–) production is controlled by SOD2, and the hydrogen peroxide (H2O2) generated by SOD2 activity and peroxynitrite (ONOO–) are scavenged mainly by PRDXs in human spermatozoa. PRDXs regulate the redox signalling necessary for sperm motility and capacitation, particularly by PRDX6. This enzyme is the first line of defence against oxidative stress to prevent lipid peroxidation and DNA oxidation by scavenging H2O2 and ONOO– through its peroxidase activity and repairing oxidized membranes by its calcium-independent phospholipase A2 activity. The success of antioxidant therapy in treating infertility resides in the proper diagnosis of the presence of oxidative stress and which type of ROS are produced. Thus, more research on the molecular mechanisms affected by oxidative stress, the development of novel diagnostic tools to identify infertile patients with oxidative stress, and randomized controlled trials are of paramount importance to generate personalized antioxidant therapy to restore male fertility.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: The impact of oxidative stress on reproduction: a focus on gametogenesis and fertilizationAitken, R John; Bromfield, Elizabeth G; Gibb, Zamira
doi: 10.1530/rep-22-0126pmid: 35929832
In briefMany aspects of the reproductive process are impacted by oxidative stress. This article summarizes the chemical nature of reactive oxygen species and their role in both the physiological regulation of reproductive processes and the pathophysiology of infertility.AbstractThis article lays out the fundamental principles of oxidative stress. It describes the nature of reactive oxygen species (ROS), the way in which these potentially toxic metabolites interact with cells and how they impact both cellular function and genetic integrity. The mechanisms by which ROS generation is enhanced to the point that the cells’ antioxidant defence mechanisms are overwhelmed are also reviewed taking examples from both the male and female reproductive system, with a focus on gametogenesis and fertilization. The important role of external factors in exacerbating oxidative stress and impairing reproductive competence is also examined in terms of their ability to disrupt the physiological redox regulation of reproductive processes. Developing diagnostic and therapeutic strategies to cope with oxidative stress within the reproductive system will depend on the development of a deeper understanding of the nature, source, magnitude, and location of such stress in order to fashion personalized treatments that meet a given patient’s clinical needs.
OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress and the long-term storage of horse spermatozoaPeña, Fernando J; Gibb, Zamira
doi: 10.1530/rep-22-0264pmid: 36255038
In briefThe growing understanding of the mechanisms regulating redox homeostasis in the stallion spermatozoa, together with its interactions with energetic metabolism, is providing new clues applicable to the improvement of sperm conservation in horses. Based on this knowledge, new extenders, adapted to the biology of the stallion spermatozoa, are expected to be developed in the near future.AbstractThe preservation of semen either by refrigeration or cryopreservation is a principal component of most animal breeding industries. Although this procedure has been successful in many species, in others, substantial limitations persist. In the last decade, mechanistic studies have shed light on the molecular changes behind the damage that spermatozoa experience during preservation. Most of this damage is oxidative, and thus in this review, we aim to provide an updated overview of recent discoveries about how stallion spermatozoa maintain redox homeostasis, and how the current procedures of sperm preservation disrupt redox regulation and cause sperm damage which affects viability, functionality, fertility and potentially the health of the offspring. We are optimistic that this review will promote new ideas for further research to improve sperm preservation technologies, promoting translational research with a wide scope for applicability not only in horses but also in other animal species and humans.