Objective: To review and present the most distinct concepts on the association of reactive oxygen species (ROS) with male reproduction. Methods: The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines were used to search PubMed, Medline, EMBASE, and the Cochrane electronic databases for studies investigating the role of oxidative stress (OS) on sperm function. Results: The literature search yielded 1857 studies, of which 1791 articles were excluded because of irrelevance of data, non-English language, non-human nature or because they were case reports or commentaries. All included studies were reviews (46), meta-analyses (one), original research studies (18) and guideline articles (one). The studies were published between 1984 and 2018. Under normal physiological conditions, ROS are vital for sperm maturation, hyperactivation, capacitation, acrosome reaction, as well as fertilisation. However, a number of endogenous and exogenous causes may induce supra-physiological levels of ROS resulting in lipid peroxidation, sperm DNA fragmentation and apoptosis, and consequently infertility. Several laboratory testing methods can be used in infertile men to diagnose OS. Treatment usually involves antioxidant supplementation and, when possible, elimination of the causative factor. Conclusion: OS is an important cause of male factor infertility. Its assessment provides essential information that can guide treatment strategies aimed at improving the male's reproductive potential. Abbreviations: bp: base-pair; CAT: catalase; LPO: lipid peroxidation; MDA: malondialdehyde; MiOXSYS: Male Infertility Oxidative System; mtDNA: mitochondrial DNA; NAD(PH): nicotinamide adenine dinucleotide (phosphate); NO: nitric oxide; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ORP: oxidation-reduction potential; OS: oxidative stress; PKA: protein kinase A; PLA2: phospholipase A2; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PUFA: poly-unsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; TAC: total antioxidant capacity; TBA: thiobarbituric acid.

https://www.tandfonline.com/doi/pdf/10.1080/2090598X.2019.1599624

Oxidative stress and sperm function: A systematic review on evaluation and management

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

/pdf/male-oxidative-stress-infertility-mosi-proposed-terminology-qk4qtg1j0q.pdf

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Differential Production of Reactive Oxygen Species by Subsets of Human Spermatozoa

Climate change is affecting biodiversity, but proximate drivers remain poorly understood. Here, we examine how experimental heatwaves impact on reproduction in an insect system. Male sensitivity to heat is recognised in endotherms, but ectotherms have received limited attention, despite comprising most of biodiversity and being more influenced by temperature variation. Using a flour beetle model system, we find that heatwave conditions (5 to 7 °C above optimum for 5 days) damaged male, but not female, reproduction. Heatwaves reduce male fertility and sperm competitiveness, and successive heatwaves almost sterilise males. Heatwaves reduce sperm production, viability, and migration through the female. Inseminated sperm in female storage are also damaged by heatwaves. Finally, we discover transgenerational impacts, with reduced reproductive potential and lifespan of offspring when fathered by males, or sperm, that had experienced heatwaves. This male reproductive damage under heatwave conditions provides one potential driver behind biodiversity declines and contractions through global warming.

/pdf/experimental-heatwaves-compromise-sperm-function-and-cause-3nj3lsr5e7.pdf

Experimental heatwaves compromise sperm function and cause transgenerational damage in a model insect.

Reactive oxygen species (ROS) have been extensively studied as a cause of male infertility. Excessive levels of ROS coupled with a deficiency in antioxidants can lead to oxidative stress (OS), which in turn can lead to nuclear and mitochondrial DNA damage, telomere shortening, epigenetic alterations and Y chromosomal microdeletions. In this review, we discuss how OS induces DNA damage and the types of DNA damage that can occur. We also briefly touch on the clinical consequences of OS-induced DNA damage.

Reactive oxygen species impact on sperm DNA and its role in male infertility.

Reactive oxygen species (ROS) play an important role in male fertility. Overproduction of reactive oxygen species (ROS) has been associated with a variety of male fertility complications, including leukocytospermia, varicocele and idiopathic infertility. The subsequent oxidative insult to spermatozoa can manifest as insufficient energy metabolism, lipid peroxidation and DNA damage, leading to loss of motility and viability. However, various studies have demonstrated that physiological amounts of ROS play important roles in the processes of spermatozoa maturation, capacitation, hyperactivation and acrosome reaction. It is therefore crucial to define and understand the delicate oxidative balance in male reproductive cells and tissues for a better understanding of both positive as well as negative impact of ROS production on the fertilizing ability. This review will discuss the specific physiological roles, mechanisms of action and effects that ROS have on the acquisition of structural integrity and physiological activity of spermatozoa.

Contemporary evidence on the physiological role of reactive oxygen species in human sperm function

Oxidative stress has been established as one of the main causes of male infertility and has been implicated in many diseases associated with infertile men. It results from high concentrations of free radicals and suppressed antioxidant potential, which may alter protein expression in seminal plasma and/or spermatozoa. In recent years, proteomic analyses have been performed to characterize the protein profiles of seminal ejaculate from men with different clinical conditions, such as high oxidative stress. The aim of the present review is to summarize current findings on proteomic studies performed in men with high oxidative stress compared with those with physiological concentrations of free radicals, to better understand the aetiology of oxidative stress-induced male infertility. Each of these studies has suggested candidate biomarkers of oxidative stress, among them are DJ-1, PIP, lactotransferrin and peroxiredoxin. Changes in protein concentrations in seminal plasma samples with oxidative stress conditions were related to stress responses and to regulatory pathways, while alterations in sperm proteins were mostly associated to metabolic responses (carbohydrate metabolism) and stress responses. Future studies should include assessment of post-translational modifications in the spermatozoa as well as in seminal plasma proteomes of men diagnosed with idiopathic infertility. Oxidative stress, which occurs due to a state of imbalance between free radicals and antioxidants, has been implicated in most cases of male infertility. Cells that are in a state of oxidative stress are more likely to have altered protein expression. The aim of this review is to better understand the causes of oxidative stress-induced male infertility. To achieve this, we assessed proteomic studies performed on the seminal plasma and spermatozoa of men with high levels of oxidative stress due to various clinical conditions and compared them with men who had physiological concentrations of free radicals. A variety of sperm and seminal plasma proteins were found to be expressed either in abundance (over-expressed) or in a lesser amount (underexpressed), while other proteins were found to be unique either to men with oxidative stress or to men with a balanced ratio of antioxidants/free radicals. Each study included in this review suggested several proteins that could possibly act as biomarkers of oxidative stress-induced male infertility, such as protein DJ-1, PIP, lactotransferrin and peroxiredoxin. Pathway analysis performed in these studies revealed that the changes in seminal plasma proteins in men with oxidative stress could be attributed to stress responses and regulatory pathways, while changes in sperm proteins were linked to stress responses and metabolic responses. Subsequent studies could look into post-translational modifications in the protein profile of men with idiopathic infertility. We hope that the information in this review will contribute to a better understanding of the main causes of idiopathic male infertility.

https://www.rbmojournal.com/article/S1472-6483(14)00130-8/pdf

Proteomics, oxidative stress and male infertility

Necrosectomy with novel morcellator device for the treatment of pancreatic walled-off necrosis: a systematic review and meta-analysis

Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.

/pdf/power-of-proteomics-in-linking-oxidative-stress-and-female-3a5dnur9gw.pdf

Power of proteomics in linking oxidative stress and female infertility.

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Contemporary evidence on the physiological role of reactive oxygen species in human sperm function

Proteomics, oxidative stress and male infertility

Necrosectomy with novel morcellator device for the treatment of pancreatic walled-off necrosis: a systematic review and meta-analysis

Power of proteomics in linking oxidative stress and female infertility.