Molecular Mechanisms of Antioxidants in Male Infertility

2013 ◽  
pp. 91-107
Author(s):  
Kathleen Hwang ◽  
Dolores J. Lamb
Keyword(s):  
Male Infertility ◽  
Molecular Mechanisms

scholarly journals Molecular mechanisms beyond glucose transport in diabetes-related male infertility

2013 ◽  
Vol 1832 (5) ◽  
pp. 626-635 ◽  
Author(s):  
M.G. Alves ◽  
A.D. Martins ◽  
L. Rato ◽  
P.I. Moreira ◽  
S. Socorro ◽  
...  
Keyword(s):  
Male Infertility ◽  
Glucose Transport ◽  
Molecular Mechanisms

The coupling apparatus of the sperm head and tail†

2020 ◽  
Vol 102 (5) ◽  
pp. 988-998
Author(s):  
Bingbing Wu ◽  
Hui Gao ◽  
Chao Liu ◽  
Wei Li
Keyword(s):  
Male Infertility ◽  
Molecular Mechanisms ◽  
Sperm Head ◽  
Evolutionary View ◽  
Fine Structures ◽  
Fierce Competition

Abstract A strong sperm head–tail coupling apparatus (HTCA) is needed to ensure the integrity of spermatozoa during their fierce competition to fertilize the egg. A lot of HTCA-specific components have evolved to strengthen the attachment of the tail to the implantation fossa at the sperm head. Defects in HTCA formation lead to acephalic spermatozoa syndrome and pathologies of some male infertility. Recent studies have provided insights into the pathogenic molecular mechanisms of acephalic spermatozoa syndrome. Here, we summarize the proteins involved in sperm neck development and focus on their roles in the formation of HTCA. In addition, we discuss the fine structures of the sperm neck in different species from an evolutionary view, highlighting the potential conservative mechanism of HTCA formation.

scholarly journals Decreased piRNAs in Infertile Semen Are Related to Downregulation of Sperm MitoPLD Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Yeting Hong ◽  
Yanqian Wu ◽  
Jianbin Zhang ◽  
Chong Yu ◽  
Lu Shen ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sperm Motility ◽  
Seminal Plasma ◽  
Molecular Mechanisms ◽  
Molecular Biomarkers ◽  
Loss Of Function ◽  
Human Seminal Plasma ◽  
High Concentrations ◽  
Tight Correlation ◽  
Infertile Patients

Currently, the molecular mechanisms underlining male infertility are still poorly understood. Our previous study has demonstrated that PIWI-interacting RNAs (piRNAs) are downregulated in seminal plasma of infertile patients and can serve as molecular biomarkers for male infertility. However, the source and mechanism for the dysregulation of piRNAs remain obscure. In this study, we found that exosomes are present in high concentrations in human seminal plasma and confirmed that piRNAs are predominantly present in the exosomal fraction of seminal plasma. Moreover, we showed that piRNAs were significantly decreased in exosomes of asthenozoospermia patients compared with normozoospermic men. By systematically screening piRNA profiles in sperms of normozoospermic men and asthenozoospermia patients, we found that piRNAs were parallelly reduced during infertility. At last, we investigated the expression of some proteins that are essential for piRNAs biogenesis in sperms and therefore identified a tight correlation between the levels of spermatozoa piRNA and MitoPLD protein, suggesting that the loss-of-function of MitoPLD could cause a severe defect of piRNA accumulation in sperms. In summary, this study identified a parallel reduction of piRNAs and MitoPLD protein in sperms of asthenozoospermia patients, which may provide pathophysiological clues about sperm motility.

scholarly journals Molecular Mechanisms Underlying the Relationship between Obesity and Male Infertility

Metabolites ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 840
Author(s):  
Federica Barbagallo ◽  
Rosita A. Condorelli ◽  
Laura M. Mongioì ◽  
Rossella Cannarella ◽  
Laura Cimino ◽  
...  
Keyword(s):  
Male Infertility ◽  
Molecular Mechanisms ◽  
Premature Mortality ◽  
Male Reproduction ◽  
Increased Risk ◽  
Inflammatory Processes ◽  
Prevalence Of Obesity ◽  
Treatment Of Obesity ◽  
The Relationship ◽  
And Oxidative Stress

In recent decades, the worldwide prevalence of obesity has risen dramatically and is currently estimated to be around 20%. Obesity is linked to an increased risk of comorbidities and premature mortality. Several studies have shown that obesity negatively impacts male fertility through various mechanisms. This review aims to investigate the molecular mechanisms through which obesity impairs male reproduction, including obesity-associated hypogonadism and its effects on spermatogenesis, chronic inflammation, and oxidative stress. Obesity negatively impacts both conventional and biofunctional sperm parameters, and it also induces epigenetic changes that can be transferred to offspring. Moreover, obesity-related diseases are linked to a dysregulation of adipocyte function and micro-environmental inflammatory processes. The dysregulated adipokines significantly influence insulin signaling, and they may also have a detrimental effect on testicular function. Sirtuins can also play an important role in inflammatory and metabolic responses in obese patients. Understanding the molecular mechanisms that are involved in obesity-induced male infertility could increase our ability to identify novel targets for the prevention and treatment of obesity and its related consequences.

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 Biallelic Mutations in WDR12 is Associated With Male Infertility With Tapered-Head Sperm

2021 ◽  
Author(s):  
juan hua ◽  
Lan Guo ◽  
Yao Yao ◽  
Yangyang Wan ◽  
Wen Hu ◽  
...  
Keyword(s):  
Male Infertility ◽  
Molecular Mechanisms ◽  
Missense Variant ◽  
Bioinformatic Analysis ◽  
Chinese Family ◽  
Intense Staining ◽  
Whole Exome ◽  
Repeat Domain ◽  
Biallelic Mutations ◽  
Pachytene Spermatocytes

Abstract Teratozoospermia is a rare disease associated with male infertility. Unfortunately, approximately 30% of the genetic causes associated with teratozoospermia remain unknown. Several recurrent genetic mutations have been reported to be associated with globozoospermia, macrozoospermia and acephalic spermatozoa, whereas the genetic basis of tapered-head sperm is relatively less well-understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12) (p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head sperm from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To further verify the effect of this variant, we analyzed WDR12 protein expression in the patient’s spermatozoa by western blot and found WDR12 to be significantly down-regulated. Also, we found that WDR12 expression is increased in pachytene spermatocytes, and intense staining was visible throughout the round spermatids in mouse testis. Based on our results, we concluded that a rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene causes teratozoospermia. These results will provide novel insights into understanding the molecular mechanisms of male infertility and will help clinicians provide accurate diagnoses.

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 Bi-allelic variants in human WDR63 cause male infertility via abnormal inner dynein arms assembly

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuai Lu ◽  
Yayun Gu ◽  
Yifei Wu ◽  
Shenmin Yang ◽  
Chenmeijie Li ◽  
...  
Keyword(s):  
Male Infertility ◽  
Protein Complex ◽  
Molecular Mechanisms ◽  
Obstructive Azoospermia ◽  
Loss Of Function ◽  
Allelic Variants ◽  
Transmission Electron ◽  
Repeat Domain ◽  
Dynein Arms ◽  
Cilia And Flagella

AbstractInner dynein arm (IDA), composed of a series of protein complex, is necessary to cilia and flagella bend formation and beating. Previous studies indicated that defects of IDA protein complex result in multiple morphological abnormalities of the sperm flagellum (MMAF) and male infertility. However, the genetic causes and molecular mechanisms in the IDAs need further exploration. Here we identified two loss-of-function variants of WDR63 in both MMAF and non-obstructive azoospermia (NOA) affected cohorts. WDR63 encodes an IDA-associated protein that is dominantly expressed in testis. We next generated Wdr63-knockout (Wdr63-KO) mice through the CRISPR-Cas9 technology. Remarkably, Wdr63-KO induced decreased sperm number, abnormal flagellar morphology and male infertility. In addition, transmission electron microscopy assay showed severely disorganized “9 + 2” axoneme and absent inner dynein arms in the spermatozoa from Wdr63-KO male mice. Mechanistically, we found that WDR63 interacted with WDR78 mainly via WD40-repeat domain and is necessary for IDA assembly. Furthermore, WDR63-associated male infertility in human and mice could be overcome by intracytoplasmic sperm injection (ICSI) treatment. In conclusion, the present study demonstrates that bi-allelic variants of WDR63 cause male infertility via abnormal inner dynein arms assembly and flagella formation and can be used as a genetic diagnostic indicator for infertility males.

scholarly journals MicroRNAs: Recent insights towards their role in male infertility and reproductive cancers

2019 ◽  
Vol 19 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Muhammad Babar Khawar ◽  
Rabia Mehmood ◽  
Nabila Roohi
Keyword(s):  
Male Infertility ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Reproductive Cancers ◽  
Post Transcriptional Regulation ◽  
Different Cell Types

Spermatogenesis is a tightly controlled, multi-step process in which mature spermatozoa are produced. Disruption of regulatory mechanisms in spermatogenesis can lead to male infertility, various diseases of male reproductive system, or even cancer. The spermatogenic impairment in infertile men can be associated with different etiologies, and the exact molecular mechanisms are yet to be determined. MicroRNAs (miRNAs) are a type of non-protein coding RNAs, about 22 nucleotides long, with an essential role in post-transcriptional regulation. miRNAs have been recognized as important regulators of various biological processes, including spermatogenesis. The aim of this review is to summarize the recent literature on the role of miRNAs in spermatogenesis, male infertility and reproductive cancers, and to evaluate their potential in diagnosis, prognosis and therapy of disease. Experimental evidence shows that aberrant expression of miRNAs affects spermatogenesis at multiple stages and in different cell types, most often resulting in infertility. In more severe cases, dysregulation of miRNAs leads to cancer. miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and reproductive system diseases. However, to exploit this potential fully, we need a better understanding of miRNA-mediated regulation of spermatogenesis, including the characterization of yet unidentified miRNAs and related regulatory mechanisms.

scholarly journals Integration and gene co-expression network analysis of scRNA-seq transcriptomes reveal heterogeneity and key functional genes in human spermatogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Najmeh Salehi ◽  
Mohammad Hossein Karimi-Jafari ◽  
Mehdi Totonchi ◽  
Amir Amiri-Yekta
Keyword(s):  
Male Infertility ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Topological Analysis ◽  
Cell Types ◽  
Round Spermatid ◽  
Functional Genes ◽  
Cell Heterogeneity ◽  
Cellular Division ◽  
Human Spermatogenesis

AbstractSpermatogenesis is a complex process of cellular division and differentiation that begins with spermatogonia stem cells and leads to functional spermatozoa production. However, many of the molecular mechanisms underlying this process remain unclear. Single-cell RNA sequencing (scRNA-seq) is used to sequence the entire transcriptome at the single-cell level to assess cell-to-cell variability. In this study, more than 33,000 testicular cells from different scRNA-seq datasets with normal spermatogenesis were integrated to identify single-cell heterogeneity on a more comprehensive scale. Clustering, cell type assignments, differential expressed genes and pseudotime analysis characterized 5 spermatogonia, 4 spermatocyte, and 4 spermatid cell types during the spermatogenesis process. The UTF1 and ID4 genes were introduced as the most specific markers that can differentiate two undifferentiated spermatogonia stem cell sub-cellules. The C7orf61 and TNP can differentiate two round spermatid sub-cellules. The topological analysis of the weighted gene co-expression network along with the integrated scRNA-seq data revealed some bridge genes between spermatogenesis’s main stages such as DNAJC5B, C1orf194, HSP90AB1, BST2, EEF1A1, CRISP2, PTMS, NFKBIA, CDKN3, and HLA-DRA. The importance of these key genes is confirmed by their role in male infertility in previous studies. It can be stated that, this integrated scRNA-seq of spermatogenic cells offers novel insights into cell-to-cell heterogeneity and suggests a list of key players with a pivotal role in male infertility from the fertile spermatogenesis datasets. These key functional genes can be introduced as candidates for filtering and prioritizing genotype-to-phenotype association in male infertility.

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