OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Reactive oxygen species in the mammalian pre-implantation embryo

Abstract

Reactive 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, GSH and clutamyl cystenine 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 aging). This review examines 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 for combating increased oxidative damage in the pre-implantation embryo through the addition of antioxidants.

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

“…Some factors, such as diet, physical activity, mental stress, and exposure to certain substances, can be "stored" in the spermatozoon as epigenetic information that can change pre-implantation metabolism, oxidative stress, and subsequent embryo quality in vitro. Therefore, the health and quality of sperm delivered at the time of fertilization play an important role [ 59 ]. It is important to know the molecular aspect and function of sperm-specific intrinsic factors.…”

Functional association between telomeres, oxidation and mitochondria

“…There is currently no consensus regarding the antioxidants that should be used or the dosage that should be used. However, it appears that the primary source of ROS for all different cell types is mitochondrial electron leakage ( 134 ). It may be helpful in this regard to enhance the development of antioxidants that particularly target the mitochondrial compartment, either by scavenging ROS within these organelles, which are known to promote ROS formation by the mitochondrial electron transport chain ( 135 , 136 ).…”

Oxidative stress and reproductive function

“…In this special issue, O'Flaherty and Scarlata (2022) expertly summarize the antioxidant systems employed by spermatozoa and highlight the versatility and importance of peroxiredoxins in this context, particularly peroxiredoxin 6. Similarly, Deluao et al (2022) provide a detailed description of the antioxidant systems employed by embryos to prevent them from entering into a state of oxidative stress, while Martin et al (2022) emphasize the importance of antioxidants in defending the functional integrity of oocytes, particularly in the context of ageing.…”

“…In addition to the use of antioxidants to treat systemic antioxidant stress in the patient as a whole, several of the papers presented in this special issue mention the potential use of antioxidants in vitro as a component of the media used to culture spermatozoa, oocytes and embryos in the context of assisted reproduction (Aitken et al 2022, Deluao et al 2022, Martin et al 2022. Such strategies appear to show great promise as a means of preserving the structural and functional integrity of gametes and embryos during the in vitro phase of their existence.…”

“…We do not yet have any consensus as to which antioxidants to add and in what concentrations they should be presented. There does however appear to be agreement that the major source of ROS in these different cell types involves electron leakage from the mitochondria (Aitken et al 2022, Deluao et al 2022, Martin et al 2022. Refining the development of antioxidants that target the mitochondrial compartment might be beneficial in this regard, either via efficient scavenging of ROS within these organelles (Koppers et al 2008, Cobley 2020, removing lipid aldehydes such as 4-hydroxynonenal, which are known to promote ROS formation by the mitochondrial electron transport chain (Aitken et al 2012, Lord et al 2015, or by controlling the mitochondrial permeability transition pore (Vercesi et al 1997, Daiber 2010.…”