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 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

scholarly journals Haploid male germ cells—the Grand Central Station of protein transport

2020 ◽  
Vol 26 (4) ◽  
pp. 474-500 ◽  
Author(s):  
Christiane Pleuger ◽  
Mari S Lehti ◽  
Jessica EM Dunleavy ◽  
Daniela Fietz ◽  
Moira K O’Bryan
Keyword(s):  
Male Infertility ◽  
Protein Transport ◽  
Model System ◽  
Sperm Head ◽  
Vesicle Transport ◽  
Future Research ◽  
Significant Percentage ◽  
Human Male ◽  
Abnormal Sperm ◽  
Haploid Male

Abstract BACKGROUND The precise movement of proteins and vesicles is an essential ability for all eukaryotic cells. Nowhere is this more evident than during the remarkable transformation that occurs in spermiogenesis—the transformation of haploid round spermatids into sperm. These transformations are critically dependent upon both the microtubule and the actin cytoskeleton, and defects in these processes are thought to underpin a significant percentage of human male infertility. OBJECTIVE AND RATIONALE This review is aimed at summarising and synthesising the current state of knowledge around protein/vesicle transport during haploid male germ cell development and identifying knowledge gaps and challenges for future research. To achieve this, we summarise the key discoveries related to protein transport using the mouse as a model system. Where relevant, we anchored these insights to knowledge in the field of human spermiogenesis and the causality of human male infertility. SEARCH METHODS Relevant studies published in English were identified using PubMed using a range of search terms related to the core focus of the review—protein/vesicle transport, intra-flagellar transport, intra-manchette transport, Golgi, acrosome, manchette, axoneme, outer dense fibres and fibrous sheath. Searches were not restricted to a particular time frame or species although the emphasis within the review is on mammalian spermiogenesis. OUTCOMES Spermiogenesis is the final phase of sperm development. It results in the transformation of a round cell into a highly polarised sperm with the capacity for fertility. It is critically dependent on the cytoskeleton and its ability to transport protein complexes and vesicles over long distances and often between distinct cytoplasmic compartments. The development of the acrosome covering the sperm head, the sperm tail within the ciliary lobe, the manchette and its role in sperm head shaping and protein transport into the tail, and the assembly of mitochondria into the mid-piece of sperm, may all be viewed as a series of overlapping and interconnected train tracks. Defects in this redistribution network lead to male infertility characterised by abnormal sperm morphology (teratozoospermia) and/or abnormal sperm motility (asthenozoospermia) and are likely to be causal of, or contribute to, a significant percentage of human male infertility. WIDER IMPLICATIONS A greater understanding of the mechanisms of protein transport in spermiogenesis offers the potential to precisely diagnose cases of male infertility and to forecast implications for children conceived using gametes containing these mutations. The manipulation of these processes will offer opportunities for male-based contraceptive development. Further, as increasingly evidenced in the literature, we believe that the continuous and spatiotemporally restrained nature of spermiogenesis provides an outstanding model system to identify, and de-code, cytoskeletal elements and transport mechanisms of relevance to multiple tissues.

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.

P–015 Characterization of ultrastructural morphology of human sperms by field-emission scanning electron microscopy using the NanoSuit method

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S So ◽  
Y Takaku ◽  
I Ohta ◽  
F Tawara ◽  
T Hariyama
Keyword(s):  
Electron Microscopy ◽  
Male Infertility ◽  
Freeze Drying ◽  
Sperm Morphology ◽  
Sperm Head ◽  
Fixation Method ◽  
Sperm Cells ◽  
Sem Observation ◽  
Optical Micrographs ◽  
Scanning Electron

Abstract Study question Can the NanoSuit method to observe sperm cells in wet conditions help treat male infertility using a field emission scanning electron microscope (FE-SEM)? Summary answer Compared with the conventional fixation method, the NanoSuit method can easily prepare FE-SEM samples without causing contraction and denaturation of human sperm cells. What is known already Evaluation of sperm morphology by optical microscopy is important for identifying male infertility. FE-SEM observation is useful for a more detailed evaluation of sperm morphology; however, a lot of the morphological information of the cells is lost by chemical fixation, dehydration, and freeze-drying. The NanoSuit method enables FE-SEM observation of unfixed cells under a high vacuum environment by electron beam polymerization of extracellular substances called NanoSuit. It has been reported that a sample prepared by the NanoSuit method retains the morphological information of live cells better than a sample prepared by the conventional fixation method. Study design, size, duration This laboratory study was conducted with informed consent and IRB approval. Semen parameters were within the WHO normal reference range. Participants/materials, setting, methods The conventional fixation method sample was prepared by fixing (glutaraldehyde and osmium), dehydration (ethanol and t-butyl alcohol), and freeze-drying. The NanoSuit method sample was introduced into the FE-SEM directly without conducting the above treatments. For observation, a JSM–7100F (JEOL, Japan) was used at an acceleration voltage of 1.0 kV. The vacuum level of the observation chamber was 10–3 to 10–6 Pa. Main results and the role of chance Sperm head segmentation (acrosome, equatorial segment, and post acrosome), midpiece, and tail including endpiece could be clearly identified in the FE-SEM sample prepared by the NanoSuit method. Transmission electron microscopy revealed the existence of a thin polymerized extra layer, the NanoSuit, on the surface of the sperm. It is suggested that the presence of the NanoSuit layer enables FE-SEM observation of the unfixed sperm. The conventional fixation method causes a statistically significant contraction in the sperm head size compared to that calculated from optical micrographs (13.5 μm2 vs. 11.6 μm2, p < 0.001). Furthermore, wheat germ agglutinin (WGA), a lectin, which is known to have the ability to bind to the sperm surface, did not bind to the fixed FE-SEM samples. This means that the original cell surface properties are lost in the fixed sperm sample. On the other hand, the FE-SEM sample prepared by the NanoSuit method did not show a statistically significant contraction of the sperm head compared to that calculated from optical micrographs (13.2 μm2 vs 12.9 μm2, p = 0.416); it also revealed a detailed binding pattern of gold-labelled WGA to the sperm surface. These results indicate that the NanoSuit method can prepare FE-SEM samples without sperm contraction and denaturation. Limitations, reasons for caution Characteristic sperm morphology in patients with male infertility should be investigated in future studies. Wider implications of the findings: The NanoSuit method does not use chemical carcinogens and can prepare an FE-SEM sample in a shorter time than the conventional fixation method. The evaluation of ultrastructural morphology of unfixed sperms by this method may be useful for the identification of new morphological features and the evaluation of male infertility. Trial registration number Not applicable

scholarly journals Essential role for SUN5 in anchoring sperm head to the tail

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Yongliang Shang ◽  
Fuxi Zhu ◽  
Lina Wang ◽  
Ying-Chun Ouyang ◽  
Ming-Zhe Dong ◽  
...  
Keyword(s):  
Male Infertility ◽  
Nuclear Membrane ◽  
Essential Role ◽  
Sperm Head ◽  
The Sun ◽  
Male Mice ◽  
Nuclear Dynamics ◽  
Intracytoplasmic Injection

SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5−/− mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility.

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