scholarly journals Role of Selective Autophagy in Spermatogenesis and Male Fertility

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2523
Author(s):  
Chunyu Lv ◽  
Xiaoli Wang ◽  
Ying Guo ◽  
Shuiqiao Yuan
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Genetic Regulation ◽  
Underlying Mechanism ◽  
Intracellular Pathogens ◽  
Selective Autophagy ◽  
Reproductive Processes ◽  
Infertile Patients ◽  
Shed Light

Autophagy is a “self-eating” process that engulfs cellular contents for their subsequent digestion in lysosomes to engage the metabolic need in response to starvation or environmental insults. According to the contents of degradation, autophagy can be divided into bulk autophagy (non-selective autophagy) and selective autophagy. Bulk autophagy degrades non-specific cytoplasmic materials in response to nutrient starvation while selective autophagy targets specific cargoes, such as damaged organelles, protein aggregates, and intracellular pathogens. Selective autophagy has been documented to relate to the reproductive processes, especially for the spermatogenesis, fertilization, and biosynthesis of testosterone. Although selective autophagy is vital in the field of reproduction, its role and the underlying mechanism have remained unclear. In this review, we focus on selective autophagy to discuss the recent advances in our understanding of the mechanism and role of selective autophagy on spermatogenesis and male fertility in mammals. Understanding the role of selective autophagy during spermatogenesis will promote the recognition of genetic regulation in male infertility, and shed light on therapies of infertile patients.

scholarly journals An Update on the Role of the Actin Cytoskeleton in Plasmodesmata: A Focus on Formins

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Diao ◽  
Shanjin Huang
Keyword(s):  
Plant Growth ◽  
Actin Cytoskeleton ◽  
Growth And Development ◽  
Cell Communication ◽  
Underlying Mechanism ◽  
Review Article ◽  
Plant Growth And Development ◽  
Shed Light

Cell-to-cell communication in plants is mediated by plasmodesmata (PD) whose permeability is tightly regulated during plant growth and development. The actin cytoskeleton has been implicated in regulating the permeability of PD, but the underlying mechanism remains largely unknown. Recent characterization of PD-localized formin proteins has shed light on the role and mechanism of action of actin in regulating PD-mediated intercellular trafficking. In this mini-review article, we will describe the progress in this area.

scholarly journals Recent advances in understanding and managing male infertility

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 670 ◽  
Author(s):  
Jonathan Fainberg ◽  
James A. Kashanian
Keyword(s):  
Male Infertility ◽  
Paternal Age ◽  
World Health ◽  
Testicular Sperm Extraction ◽  
Male Factor Infertility ◽  
Male Factor ◽  
Lifestyle Choices ◽  
Health Organization ◽  
Shed Light

Infertility is a prevalent condition affecting an estimated 70 million people globally. The World Health Organization estimates that 9% of couples worldwide struggle with fertility issues and that male factor contributes to 50% of the issues. Male infertility has a variety of causes, ranging from genetic mutations to lifestyle choices to medical illnesses or medications. Recent studies examining DNA fragmentation, capacitation, and advanced paternal age have shed light on previously unknown topics. The role of conventional male reproductive surgeries aimed at improving or addressing male factor infertility, such as varicocelectomy and testicular sperm extraction, have recently been studied in an attempt to expand their narrow indications. Despite advances in the understanding of male infertility, idiopathic sperm abnormalities still account for about 30% of male infertility. With current and future efforts examining the molecular and genetic factors responsible for spermatogenesis and fertilization, we may be better able to understand etiologies of male factor infertility and thus improve outcomes for our patients.

scholarly journals A de novo paradigm for male infertility

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
M. S. Oud ◽  
R. M. Smits ◽  
H. E. Smith ◽  
F. K. Mastrorosa ◽  
G. S. Holt ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
Missense Mutations ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Systematic Analysis ◽  
Significant Enrichment ◽  
Infertile Patients

AbstractDe novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10−5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10−4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.

scholarly journals Ccdc38 is required for sperm flagellum biogenesis and male fertility in mouse

2022 ◽  
Author(s):  
Ruidan Zhang ◽  
Wei Li ◽  
Li Yuan ◽  
Fei Gao ◽  
Bingbing Wu ◽  
...  
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Essential Role ◽  
Coiled Coil ◽  
Male Mice ◽  
Sperm Tail ◽  
Mouse Sperm ◽  
Sperm Flagellum ◽  
Coiled Coil Domain

Sperm flagellum is essential for male fertility, defects in flagellum biogenesis are associated with male infertility. Deficiency of CCDC42 is associated with malformation of the mouse sperm flagella. Here, we find that the testis-specific expressed protein CCDC38 (coiled coil domain containing 38) interacts with CCDC42 and localizes on manchette and sperm tail during spermiogenesis. Inactivation of CCDC38 in male mice results in distorted manchette, multiple morphological abnormalities of the flagella (MMAF) of spermatozoa, and eventually male sterility. Furthermore, we find that CCDC38 interacts with intra-flagellar transport protein 88 (IFT88) as well as the outer dense fibrous 2 (ODF2), and its depletion reduces the transportation of ODF2 to flagellum. Altogether, our results uncover the essential role of CCDC38 during sperm flagellum biogenesis, and suggesting the defects of these genes might be associated with male infertility in human being.

scholarly journals Mitochondrial Functionality in Male Fertility: From Spermatogenesis to Fertilization

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 98
Author(s):  
Yoo-Jin Park ◽  
Myung-Geol Pang
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Ros Generation ◽  
Male Reproductive Tract ◽  
Proteomic Data ◽  
Epididymal Maturation ◽  
Sperm Dna

Mitochondria are structurally and functionally distinct organelles that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), to provide energy to spermatozoa. They can also produce reactive oxidation species (ROS). While a moderate concentration of ROS is critical for tyrosine phosphorylation in cholesterol efflux, sperm–egg interaction, and fertilization, excessive ROS generation is associated with male infertility. Moreover, mitochondria participate in diverse processes ranging from spermatogenesis to fertilization to regulate male fertility. This review aimed to summarize the roles of mitochondria in male fertility depending on the sperm developmental stage (from male reproductive tract to female reproductive tract). Moreover, mitochondria are also involved in testosterone production, regulation of proton secretion into the lumen to maintain an acidic condition in the epididymis, and sperm DNA condensation during epididymal maturation. We also established the new signaling pathway using previous proteomic data associated with male fertility, to understand the overall role of mitochondria in male fertility. The pathway revealed that male infertility is associated with a loss of mitochondrial proteins in spermatozoa, which induces low sperm motility, reduces OXPHOS activity, and results in male infertility.

scholarly journals Metformin Improves Fertility in Obese Males by Alleviating Oxidative Stress-Induced Blood-Testis Barrier Damage

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Jifeng Ye ◽  
Dandan Luo ◽  
Xiaolin Xu ◽  
Mingqi Sun ◽  
Xiaohui Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
High Fat Diet ◽  
Male Fertility ◽  
Underlying Mechanism ◽  
High Fat ◽  
Metabolic Disturbances ◽  
Related Proteins ◽  
Obese Male ◽  
Blood Testis Barrier

Background/Aims. Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males. Methods. An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor κB (NF-κB) was assessed by immunofluorescence. Results. High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-κB activity in Sertoli cells (SCs). Conclusion. Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.

scholarly journals Catalase as a Molecular Target for Male Infertility Diagnosis and Monitoring: An Overview

Antioxidants ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 78
Author(s):  
Nuria Rubio-Riquelme ◽  
Natalia Huerta-Retamal ◽  
María José Gómez-Torres ◽  
Rosa María Martínez-Espinosa
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Biochemical Analysis ◽  
Potential Role ◽  
Current Knowledge ◽  
Fertility Restoration ◽  
Molecular Target ◽  
Human Beings ◽  
Good Target

Catalase (CAT) stands out as one of the most efficient natural enzymes when catalysing the split of H2O2 into H2O and O2; H2O2 is one of the reactive oxygen species (ROS) involved in oxidative stress, a process closely related to aging and several health disorders or diseases like male infertility. Some studies have correlated H2O2 with male infertility and catalase with fertility restoration. However, the number of studies conducted with human beings remains scarce. Considering the use of CAT as a molecular target for biochemical analysis, this review summarises the current knowledge on how CAT influences human beings’ male fertility. Thus, three different databases were consulted—Scopus, PubMed and WOS—using single keywords and combinations thereof. A total of 40,823 articles were identified. Adopting inclusion and exclusion criteria, a final database of 197 articles served to conduct this work. It follows from this analysis that CAT could play an important role in male fertility and could become a good target for male infertility diagnosis and monitoring. However, that potential role of CAT as a tool in diagnosis must be confirmed by clinical trials. Finally, guidelines are suggested to reinforce the use of CAT in daily clinical tests for male fertility diagnosis and monitoring.

scholarly journals Tachykinins and Kisspeptins in the Regulation of Human Male Fertility

2019 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Víctor Blasco ◽  
Francisco M. Pinto ◽  
Cristina González-Ravina ◽  
Esther Santamaría-López ◽  
Luz Candenas ◽  
...  
Keyword(s):  
Male Infertility ◽  
Male Fertility ◽  
Animal Species ◽  
Reproductive Age ◽  
Diagnosis And Treatment ◽  
Male Factor ◽  
Human Male ◽  
Human Fertility ◽  
The World

Infertility is a global disease affecting one out of six couples of reproductive age in the world, with a male factor involved in half the cases. There is still much to know about the regulation of human male fertility and thus we decided to focus on two peptide families that seem to play a key role in this function: tachykinins and kisspeptins. With this aim, we conducted an exhaustive review in order to describe the role of tachykinins and kisspeptins in human fertility and their possible implications in infertility etiopathogenesis. Many advances have been made to elucidate the roles of these two families in infertility, and multiple animal species have been studied, including humans. All of this knowledge could lead to new advances in male infertility diagnosis and treatment, but further research is needed to clarify all the implications of tachykinins and kisspeptins in fertility.

scholarly journals Impact of Heavy Metals on Human Male Fertility—An Overview

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1473
Author(s):  
Andrea López-Botella ◽  
Irene Velasco ◽  
Maribel Acién ◽  
Paula Sáez-Espinosa ◽  
José-Luis Todolí-Torró ◽  
...  
Keyword(s):  
Heavy Metals ◽  
Heavy Metal ◽  
Male Infertility ◽  
Male Fertility ◽  
Current Knowledge ◽  
Metal Exposure ◽  
Heavy Metal Exposure ◽  
Human Male ◽  
Heavy Metal Assessment

Heavy metals are endocrine disruptors which interfere with processes mediated by endogenous hormones of the organism, negatively affecting endocrine functions. Some studies have correlated heavy metal exposure with male infertility. However, the number of studies conducted on humans are limited. Therefore, the aim of this study is to summarize the current knowledge on how heavy metals influence human male fertility. Hence, three distinct databases were consulted—PubMed, Scopus and Web of Science—using single keywords and combinations of them. The total number of identified articles was 636. Nevertheless, by using the inclusion and exclusion criteria, 144 articles were finally included in this work. Results display that the development of adequate instruments for heavy metal assessment may play an important function in human male fertility diagnosis and treatment. Furthermore, clinical trials could be useful to confirm the role of heavy metals in human male fertility diagnosis. Overall, further research is required to fully understand the molecular and cellular basis of the influence of environmental and occupational exposure to heavy metals on human male infertility and reproductive outcomes.

scholarly journals Anthropometric Variables as Predictors of Semen Parameters and Fertility Outcomes after Varicocelectomy

2020 ◽  
Vol 9 (4) ◽  
pp. 1160
Author(s):  
Ramy Abou Ghayda ◽  
Robert Zakhia El-Doueihi ◽  
Jun Young Lee ◽  
Muhammad Bulbul ◽  
Nassib Abou Heidar ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Male Infertility ◽  
Treatment Option ◽  
Semen Parameters ◽  
Total Count ◽  
Younger Patients ◽  
Scientific Debate ◽  
Low Bmi ◽  
Infertile Patients

Varicocele is the most common correctable male infertility factor and varicocelectomy has been a mainstay in the management of infertility. However, the role of varicocelectomy as a treatment option has been controversial, and the scientific debate around it is still ongoing. Our study aimed to explore the role of anthropometric variables of infertile patients and their relation to sperm parameters following varicocelectomy. The outcome of 124 infertile patients who underwent open sub-inguinal varicocelectomy by a single surgeon over the last ten years was studied. Post varicocelectomy, four semen parameters (volume, total count, motility, and morphology) were analyzed and adjusted according to anthropometric variables including age, varicocele grade, and body mass index (BMI) of patients. Total count and motility were significantly improved after surgery. Varicocelectomy improved semen parameters, notably the count and the motility, especially in younger patients, lower grades of varicocele patients, and low BMI patients. In addition, BMI was positively correlated with volume in pre-varicocelectomy and post-varicocelectomy.

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