Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation

Diabetic neuropathy, with its major clinical sequels, notably neuropathic pain, foot ulcers, and autonomic dysfunction, is associated with substantial morbidity, increased risk of mortality, and reduced quality of life. Despite its major clinical impact, diabetic neuropathy remains underdiagnosed and undertreated. Moreover, the evidence supporting a benefit for causal treatment is weak at least in patients with type 2 diabetes, and current pharmacotherapy is largely limited to symptomatic treatment options. Thus, a better understanding of the underlying pathophysiology is mandatory for translation into new diagnostic and treatment approaches. Improved knowledge about pathogenic pathways implicated in the development of diabetic neuropathy could lead to novel diagnostic techniques that have the potential of improving the early detection of neuropathy in diabetes and prediabetes to eventually embark on new treatment strategies. In this review, we first provide an overview on the current clinical aspects and illustrate the pathogenetic concepts of (pre)diabetic neuropathy. We then describe the biomarkers emerging from these concepts and novel diagnostic tools and appraise their utility in the early detection and prediction of predominantly distal sensorimotor polyneuropathy. Finally, we discuss the evidence for and limitations of the current and novel therapy options with particular emphasis on lifestyle modification and pathogenesis-derived treatment approaches. Altogether, recent years have brought forth a multitude of emerging biomarkers reflecting different pathogenic pathways such as oxidative stress and inflammation and diagnostic tools for an early detection and prediction of (pre)diabetic neuropathy. Ultimately, these insights should culminate in improving our therapeutic armamentarium against this common and debilitating or even life-threatening condition.

Emerging Biomarkers, Tools, and Treatments for Diabetic Polyneuropathy

Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.

https://link.springer.com/content/pdf/10.1007/s00702-020-02145-7.pdf

Challenges of neuropathic pain: focus on diabetic neuropathy.

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Current evidence links oxidative stress (OS) to male infertility, reduced sperm motility, sperm DNA damage and increased risk of recurrent abortions and genetic diseases. A review of PubMed, Medline, Google Scholar, and Cochrane review databases of published articles from years 2000–2018 was performed focusing on physiological and pathological consequences of reactive oxygen species (ROS), sperm DNA damage, OS tests, and the association between OS and male infertility, pregnancy and assisted reproductive techniques outcomes. Generation of ROS is essential for reproductive function, but OS is detrimental to fertility, pregnancy, and genetic status of the newborns. Further, there is a lack of consensus on selecting OS test, type, and duration of antioxidants treatment as well as on the target patients group. Developing advanced diagnostic and therapeutic options for OS is essential to improve fertility potential and limit genetic diseases transmitted to offspring.

Role of Oxidative Stress in Male Infertility: An Updated Review.

It has been estimated that approximately 15% of reproductive-age couples suffer from infertility. Male factors contribute to almost half of infertility cases, and in many patients the underlying cause of oligoasthenoteratozoospermia is unknown. Accumulating evidence suggests that oxidative stress plays a role as a contributing factor to male infertility, and reactive oxygen species have been shown to impair sperm function and motility and to damage sperm membrane and DNA. Therefore, this review explored the evidence provided by studies published from 2002 to 2017 on the impact of oral antioxidants (vitamin C, vitamin E, L-carnitine, coenzyme Q10, zinc, selenium, and pentoxifylline) on seminal fluid parameters in men with idiopathic oligoasthenoteratozoospermia. Most of the studies were randomized controlled studies that investigated the effect of single or combined antioxidants and reported improvements in at least one semen parameter. The most noteworthy effect that was found was that the use of multiple antioxidants increased sperm motility and concentration. Nonetheless, there is a lack of agreement on the dose, the duration of treatment, and whether individual or combined oral antioxidants should be used. Therefore, the current review provides evidence supporting the use of oral antioxidants in the treatment of infertile men with idiopathic oligoasthenoteratozoospermia.

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The effects of oral antioxidants on the semen of men with idiopathic oligoasthenoteratozoospermia.

PURPOSE Oxidative stress and sperm DNA fragmentation (SDF) are potential contributing factors for idiopathic male infertility. Coenzyme Q10 (CoQ10) have been reported to be effective in the treatment of idiopathic male infertility, in general, owing to its antioxidant properties. Thus, the present study intends to investigate the effects of CoQ10 therapy on semen parameters, oxidative stress markers and SDF in infertile men, specifically with idiopathic oligoasthenozoospermia (OA). MATERIALS AND METHODS In this case-control study, sixty-five infertile patients with idiopathic OA and forty fertile men (control) were included. All participants underwent semen analysis based on the World Health Organization guidelines (5th edition, 2010). Patients received CoQ10 at the dose of 200 mg/d orally for three months. Seminal plasma CoQ10, total antioxidant capacity (TAC), total reactive oxygen species (ROS), glutathione peroxidase (GPx), and SDF levels were measured in controls (baseline) and infertile patients pre- and post-CoQ10 treatment. RESULTS CoQ10 treatment for three months significantly improved sperm concentration (p<0.05), progressive motility (p<0.05), total motility (p<0.01), seminal fluid CoQ10 concentration (p<0.001), TAC (p<0.001), and GPx (p<0.001) levels in infertile men with OA. Further, ROS level (p<0.05) and SDF percentage (p<0.001) were reduced in OA patients as compared to the baseline. CoQ10 levels also correlated positively with sperm concentration (r=0.48, p=0.01) and total motility (r=0.59, p=0.003) while a negative correlation was recorded between SDF and sperm motility (r=-0.54, p=0.006). CONCLUSIONS CoQ10 supplementation for three months could improve semen parameters, oxidative stress markers and reduce SDF in infertile men with idiopathic OA.

Coenzyme Q10 Improves Sperm Parameters, Oxidative Stress Markers and Sperm DNA Fragmentation in Infertile Patients with Idiopathic Oligoasthenozoospermia.

Oxidative stress (OS) is a key contributing factor in 30–80% of male infertility cases To date, several antioxidant treatments have been put forth to manage OS-induced male infertility This study intended to elucidate the impact of coenzyme Q10 (CoQ10) and selenium on seminal fluid parameters and antioxidant status in infertile men with idiopathic oligoasthenoteratospermia (OAT) In this prospective study, 70 patients with idiopathic OAT were randomly allocated to receive CoQ10 (200 mg/day) or selenium (200 μg/day) for 3 months Semen quality parameters (following WHO guidelines, 5th edition), total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activities were compared before and after the treatment The results of the study showed an increase in sperm concentration with CoQ10 treatment (p < 001) as well as increased progressive sperm motility (p < 001 and p < 005) and total sperm motility (p < 001 and p < 005) with CoQ10 and selenium treatment respectively There was also a significant improvement in TAC (p < 001 and p < 005) and SOD (p < 001 and p < 005) following treatment with CoQ10 and selenium respectively while CAT improved only with CoQ10 therapy (p < 005) Sperm concentration, motility, and morphology also correlated significantly with TAC, SOD, and CAT (r = 037–076) In conclusion, treatment with CoQ10 (200 mg) or selenium (200 μg) could improve sperm concentration, motility, and antioxidant status in infertile men with idiopathic OAT with CoQ10 providing the higher improvement

Ahmed T Alahmar

Papers

Role of Oxidative Stress in Male Infertility: An Updated Review.

The effects of oral antioxidants on the semen of men with idiopathic oligoasthenoteratozoospermia.

Coenzyme Q10 Improves Sperm Parameters, Oxidative Stress Markers and Sperm DNA Fragmentation in Infertile Patients with Idiopathic Oligoasthenozoospermia.

Impact of Coenzyme Q10 and Selenium on Seminal Fluid Parameters and Antioxidant Status in Men with Idiopathic Infertility.

NerveCheck: An inexpensive quantitative sensory testing device for patients with diabetic neuropathy