scholarly journals Prm2 deficiency triggers a Reactive Oxygen Species (ROS)-mediated destruction cascade during epididymal sperm maturation in mice

2020 ◽  
Author(s):  
Simon Schneider ◽  
Farhad Shakeri ◽  
Christian Trötschel ◽  
Lena Arévalo ◽  
Alexander Kruse ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Molecular Mechanisms ◽  
Sperm Maturation ◽  
Preimplantation Embryos ◽  
Sperm Function ◽  
Epididymal Sperm ◽  
Small Proteins ◽  
Infertile Men ◽  
New Treatment

AbstractProtamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Prm2-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like SOD1 and PRDX5, ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.Significance statementSexual reproduction requires the successful fertilization of female eggs by male sperm. The generation of functional sperm is a complex, multi-step differentiation process known as spermatogenesis that takes places in the male testis. One important step for physiological sperm function is the incorporation of small proteins, known as protamines into the DNA. Defects within this process are common causes of male infertility. However, the underlying molecular mechanisms still remain largely unknown, thus preventing targeted therapies. Here, we identify the molecular cascade being initiated in protamine-deficient murine sperm that ultimately impedes fertilization. Our findings have broad implications for the development of new treatment options for infertile men with faulty protamination that seek medical advice.

scholarly journals Protamine-2 Deficiency Initiates a Reactive Oxygen Species (ROS)-Mediated Destruction Cascade during Epididymal Sperm Maturation in Mice

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1789
Author(s):  
Simon Schneider ◽  
Farhad Shakeri ◽  
Christian Trötschel ◽  
Lena Arévalo ◽  
Alexander Kruse ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blastocyst Stage ◽  
Sperm Maturation ◽  
Preimplantation Embryos ◽  
Dna Integrity ◽  
Label Free ◽  
Epididymal Sperm ◽  
Treatment Regimens ◽  
Protamine 2

Protamines are the safeguards of the paternal sperm genome. They replace most of the histones during spermiogenesis, resulting in DNA hypercondensation, thereby protecting its genome from environmental noxa. Impaired protamination has been linked to male infertility in mice and humans in many studies. Apart from impaired DNA integrity, protamine-deficient human and murine sperm show multiple secondary effects, including decreased motility and aberrant head morphology. In this study, we use a Protamine-2 (Prm2)-deficient mouse model in combination with label-free quantitative proteomics to decipher the underlying molecular processes of these effects. We show that loss of the sperm’s antioxidant capacity, indicated by downregulation of key proteins like Superoxide dismutase type 1 (SOD1) and Peroxiredoxin 5 (PRDX5), ultimately initiates an oxidative stress-mediated destruction cascade during epididymal sperm maturation. This is confirmed by an increased level of 8-OHdG in epididymal sperm, a biomarker for oxidative stress-mediated DNA damage. Prm2-deficient testicular sperm are not affected and initiate the proper development of blastocyst stage preimplantation embryos in vitro upon intracytoplasmic sperm injection (ICSI) into oocytes. Our results provide new insight into the role of Prm2 and its downstream molecular effects on sperm function and present an important contribution to the investigation of new treatment regimens for infertile men with impaired protamination.

scholarly journals Epididymal cysteine-rich secretory proteins are required for epididymal sperm maturation and optimal sperm function

2018 ◽  
Vol 24 (3) ◽  
pp. 111-122 ◽  
Author(s):  
Jinghua Hu ◽  
D Jo Merriner ◽  
Anne E O’Connor ◽  
Brendan J Houston ◽  
Luc Furic ◽  
...  
Keyword(s):  
Sperm Maturation ◽  
Secretory Proteins ◽  
Sperm Function ◽  
Epididymal Sperm

scholarly journals Impact of oxidative stress on semen parameters in normozoospermic infertile men: a case–control study

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Ayad Palani ◽  
Ahmed Alahmar
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Male Infertility ◽  
Seminal Plasma ◽  
Case Control Study ◽  
Case Control ◽  
Semen Parameters ◽  
Infertile Men ◽  
Total Antioxidant ◽  
Control Study

Abstract Background Oxidative stress has been implicated in male infertility through decrease in sperm quality. However, men with normal semen parameters (normozoospermia) may be unable to fertilize their partners even when they have normal sperm function. Thus, they would be considered infertile. The purpose of this study was to investigate the role of oxidative stress in the pathogenesis of unexplained male infertility. Methods In this case–control study, infertile men with normozoospermia (n = 46) and fertile control group (n = 21) underwent seminal fluid analyses according to WHO 2010 criteria. Serum and seminal plasma levels of total antioxidant capacity (TAC), glutathione, malondialdehyde, uric acid and albumin were also measured using colorimetric methods. Results The level of total antioxidant capacity in both serum and seminal plasma was significantly lower in normozoospermic infertile men in comparison with fertile group (p < 0.0001). However, no significant differences were observed in serum and seminal plasma levels of glutathione, uric acid, albumin and malondialdehyde between infertile and fertile groups. Conclusion Low TAC level induces oxidative stress and consequently causes sperm dysfunction and male infertility. Estimation of TAC can be a useful tool in the diagnosis of male infertility. Antioxidant supplementation should be considered in the treatment of oxidative stress-induced male infertility.

scholarly journals Seminal Plasma Proteomic Biomarkers of Oxidative Stress

2020 ◽  
Vol 21 (23) ◽  
pp. 9113
Author(s):  
Rossella Cannarella ◽  
Andrea Crafa ◽  
Federica Barbagallo ◽  
Laura M. Mongioì ◽  
Rosita A. Condorelli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Seminal Plasma ◽  
Molecular Mechanisms ◽  
Seminal Fluid ◽  
Accessory Gland ◽  
Male Accessory Gland ◽  
Abnormal Sperm ◽  
Clinical Conditions ◽  
Biomarkers Of Oxidative Stress

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30–80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms “seminal fluid proteome”, “seminal plasma proteome”, “oxidative stress”, and “sperm oxidative stress” were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.

scholarly journals Efficacy of Antioxidant Supplementation on Conventional and Advanced Sperm Function Tests in Patients with Idiopathic Male Infertility

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 219 ◽  
Author(s):  
Mohamed Arafa ◽  
Ashok Agarwal ◽  
Ahmad Majzoub ◽  
Manesh Kumar Panner Selvam ◽  
Saradha Baskaran ◽  
...  
Keyword(s):  
Male Infertility ◽  
Fertility Treatment ◽  
Semen Parameters ◽  
Unknown Etiology ◽  
Sperm Function ◽  
Sperm Dna Fragmentation ◽  
Idiopathic Male Infertility ◽  
Progressive Motility ◽  
Infertile Men ◽  
Function Tests

Antioxidants are used in the empirical treatment of infertile men. The aim of this study was to evaluate the effects of antioxidant therapy on conventional semen parameters and advanced sperm function tests in men seeking fertility treatment. A total of 148 infertile men of unknown etiology were divided into idiopathic (n = 119) and unexplained male infertility (UMI; n = 29). All participants were treated with the antioxidant supplement ‘FH PRO for Men’ for a period of three months. Compared with pretreatment results, there was a significant improvement in conventional semen parameters including sperm concentration, total and progressive motility and normal morphology, and seminal oxidation reduction potential (ORP), and sperm DNA fragmentation (SDF) in idiopathic infertile men. The changes were more prominent in idiopathic infertile men positive for ORP and SDF. UMI patients showed an improvement in progressive motility, ORP, and SDF after antioxidant treatment. Statistical analysis revealed that the efficacy of FH PRO for Men was significant in idiopathic male infertility compared with UMI. Treatment of idiopathic male infertility patients with the FH PRO for Men antioxidant regimen for three months resulted in a significant improvement in conventional semen parameters and sperm function. Therefore, FH PRO for Men offers promise for the medical treatment of idiopathic male infertility.

Administration of Antioxidants in the Infertile Male: When it may have a Beneficial Effect?.

2020 ◽  
Vol 26 ◽  
Author(s):  
Zsolt Kopa ◽  
Marton Keszthelyi ◽  
Nikolaos Sofikitis
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Membrane Damage ◽  
Live Birth Rate ◽  
Redox Status ◽  
Antioxidant Systems ◽  
Sperm Function ◽  
Antioxidant Treatment ◽  
Reductive Stress ◽  
Pre Treatment

Background: Reactive Oxygen Species (ROS) are required for intact spermatogenesis and sperm function, but excessive levels will cause oxidative stress, impairing sperms and sperm function due to membrane damage and DNA fragmentation. Objective: Theoretically, antioxidant supplementation may act as a protecting system against free radicals. Since infertile males have higher levels of ROS, nutritional supplements are widely used for protecting sperms. In the recent review authors summarize the most recent data regarding the effect of antioxidant treatment and draw an attention of the limitations of antioxidant use in male infertility. Methods: The recent review gives an update of antioxidant treatment in male infertility. Results: Improvement of sperm parameters was reported in the majority of studies. Comparing different antioxidants versus placebo showed low certainty of evidence with a serious risk of bias, and there is a lack regarding certain doses, pregnancy rate, and live birth rate outcomes. Various clinical studies and randomized control trials reported even negative outcomes. Conflicting findings lead the attention to the study of biochemical features of the oxidant vs. antioxidant equilibrium. Higher exposure to antioxidants will result in „reductive stress”, which has harmful effects on sperm function, moreover can negatively influence embryo development. Reductive stress is as dangerous as oxidative stress and may act as a cause of different human pathologies. Conclusion: An intact balance of oxidant and antioxidant systems is required to normal sperm function. No guideline exists for the antioxidant dose regimen and treatment duration. Overdosing can result in reductive stress, which is also harmful to fertility and can cause several diseases. Assessment of the pre-treatment redox status can be recommended before the administration of exogenous antioxidants.

Sperm function and seminal oxidative stress as tools to identify sperm pathologies in infertile men

2010 ◽  
Vol 93 (1) ◽  
pp. 297-300 ◽  
Author(s):  
T. Ramya ◽  
Man Mohan Misro ◽  
Devabrata Sinha ◽  
Deoki Nandan
Keyword(s):  
Oxidative Stress ◽  
Sperm Function ◽  
Infertile Men

scholarly journals Coenzyme Q10,α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Anna Gvozdjáková ◽  
Jarmila Kucharská ◽  
Jozef Dubravicky ◽  
Viliam Mojto ◽  
Ram B. Singh
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Blood Plasma ◽  
Seminal Fluid ◽  
Sperm Density ◽  
Infertile Men ◽  
Main Factors ◽  
Metabolic Biomarkers ◽  
And Oxidative Stress ◽  
In Blood Plasma

Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzymeQ10,  CoQ10-TOTAL,γ, andα-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations ofCoQ10-TOTAL(ubiquinone + ubiquinol) andα-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress,CoQ10-TOTAL, andα-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

scholarly journals Hyperviscous Semen Causes Poor Sperm Quality and Male Infertility through Induction of Oxidative Stress

2019 ◽  
Vol 13 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Asghar Beigi Harchegani ◽  
Hamid Rahmani ◽  
Eisa Tahmasbpour ◽  
Alireza Shahriary
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Molecular Mechanisms ◽  
Semen Quality ◽  
Sperm Quality ◽  
Fertilization Rate ◽  
Cellular Mechanisms ◽  
Vitro Fertilization ◽  
Randomized Controlled Studies

Background/Aims: Semen hyperviscosity (SHV) is one of the significant factors involved in poor semen quality and male infertility. It also leads major problems during assisted reproduction techniques and in vitro fertilization process. Although influence of SHV on sperm quality, fertilization rate and male infertility have been widely considered, molecular and cellular mechanisms for these abnormalities are not well understood. In this review, we aimed to discuss the proposed cellular and molecular mechanisms of SHV on male reproductive system, the importance of oxidative stress (OS) and the mechanisms by which SHV induces OS and impairment of other antioxidants. Methods: A PubMed/Medline and EM-BASE search was performed using keywords: “hyperviscosity semen”, “oxidative stress”, and “male infertility”. Conclusion: OS induced by reactive oxygen species can be considered as a major mechanism in patients with hyperviscosity semen that is associated with DNA fragmentation, lipid peroxida-tion and sperm membrane disintegrity, apoptosis, depletion of antioxidants, and subsequently poor sperm quality and male infertility. Therefore, antioxidant therapy may improve main pathological effects of hyperviscosity semen, especially oxidative damages and inflammation, on sperm quality and function. Further, randomized controlled studies are necessary to confirm these results and make a comparison between effects of various antioxidants such as N-acethyl-cysteine and Curcumin on fertility problem in patients with hyperviscous semen.

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