scholarly journals AXDND1, a novel testis-enriched gene, is required for spermiogenesis and male fertility

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qian Ma ◽  
Congcong Cao ◽  
Changshui Zhuang ◽  
Xiaomin Luo ◽  
Xiaofeng Li ◽  
...  
Keyword(s):  
Male Fertility ◽  
Dynamic Structure ◽  
Obstructive Azoospermia ◽  
Testis Size ◽  
Deleterious Mutations ◽  
Regulatory Pathways ◽  
Germ Cell Apoptosis ◽  
Sperm Flagellum ◽  
Complex Process ◽  
Gene Regulations

AbstractSpermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non‐obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.

scholarly journals Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice

PLoS Genetics ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. e1008585 ◽  
Author(s):  
Akane Morohoshi ◽  
Haruhiko Miyata ◽  
Keisuke Shimada ◽  
Kaori Nozawa ◽  
Takafumi Matsumura ◽  
...  
Keyword(s):  
Male Fertility ◽  
Complex Component ◽  
Sperm Flagellum ◽  
Regulatory Complex

scholarly journals 2018

2017 ◽  
Vol 1 (S1) ◽  
pp. 42-42
Author(s):  
Alexandra Joelle Greenberg ◽  
Nathan P. Staff ◽  
Anthony Windebank
Keyword(s):  
Regenerative Medicine ◽  
Early Stage ◽  
Primary Objective ◽  
Regulatory Pathways ◽  
Human Trials ◽  
Complex Process ◽  
Biomedical Scientist ◽  
Institutional Resources ◽  
Study Population ◽  
Translational Process

OBJECTIVES/SPECIFIC AIMS: Translating conventional and regenerative medicine strategies from the research laboratory into the clinic is a complex process that can delay bringing novel therapies to the patient. Navigating the increasingly complex regulation surrounding cell-based and combination product technologies is a major challenge for the translational biomedical scientist. To this end, Mayo Clinic created a new position, the “Translational Integrator,” as part of the cGMP Biomaterials Facility in the Center for Regenerative Medicine. METHODS/STUDY POPULATION: The Translational Integrator educates investigators about FDA standards and regulatory pathways; determines where the product is on the translational spectrum; works to understand the science behind the product; determines what additional studies may be needed; supports investigators in preparing for FDA communications and submissions; and educates researchers about institutional resources and funding mechanisms needed to move their product into manufacturing and trials. A primary objective is to meet investigators at an early stage in product development to avoid conducting potentially redundant work to meet regulatory requirements. RESULTS/ANTICIPATED RESULTS: Robust training in clinical and translational research methodology enables the integrator to facilitate the collaboration necessary between investigators, clinicians, institutional resources, regulators and funders to move products towards FDA IND/IDE approval and first-in-human trials. It is an iterative process using technology/translational readiness criteria, project management and review by subject matter experts that is highly interactive and customized to each project. Current projects include topics in orthopedic surgery and ENT. In creating and refining this position, several key lessons have been learned. DISCUSSION/SIGNIFICANCE OF IMPACT: First, the Translational Integrator must undergo constant reflection and assessment of investigator needs, which requires flexibility and understanding that their role may change in the context of each product. Second, the support that the Translational Integrator provides can shift the mindset of the investigator from being averse to engaging in the translational process to eager to move their product forward. Finally, for the investigator who does not personally want to move their work into first-in-human trials, establishing connections to intellectual property generation and licensing may support movement of their findings into patients.

scholarly journals Human testicular peritubular cells: more than meets the eye

Reproduction ◽  
2013 ◽  
Vol 145 (5) ◽  
pp. R107-R116 ◽  
Author(s):  
Artur Mayerhofer
Keyword(s):  
Male Fertility ◽  
Morphological Changes ◽  
Culture Method ◽  
Seminiferous Tubules ◽  
Potential Contribution ◽  
Obstructive Azoospermia ◽  
Testicular Cells ◽  
Cell Niche ◽  
High Degree ◽  
Peritubular Cells

In healthy men, several layers of inconspicuously flat cells and extracellular matrix (ECM) proteins build the wall of the seminiferous tubules. The cells of this wall, peritubular cells, are not well characterized. They are smooth-muscle-like and contractile and transport immotile sperm, a function important for male fertility. However, their full functional importance, especially their potential contribution to the paracrine regulation of the male gonad, is unknown. In men with impaired spermatogenesis, the architecture of the tubular wall is frequently altered. Deposits of ECM and morphological changes of peritubular cells imply that functions of peritubular cells may be fundamentally altered. To be able to study human peritubular cells and their functions, a culture method was established. It is based on small biopsies of patients with obstructive azoospermia but normal spermatogenesis (human testicular peritubular cells, HTPCs) and non-obstructive azoospermia, impaired spermatogenesis, and testicular fibrosis (HTPCFs). Results obtained from cellular studies and parallel examinations of biopsies provide insights into the repertoire of the secretion products, contractile properties, and plasticity of human peritubular cells. They produce ECM components, including the proteoglycan decorin, which may influence paracrine signaling between testicular cells. They may contribute to the spermatogonial stem cell niche via secreted factors. They are regulated by mast cell and macrophage products, and in response produce factors that can fuel inflammatory changes. They possess a high degree of plasticity, which results in hypertrophy and loss of contractile abilities. The data collectively indicate important roles of inconspicuous testicular peritubular cells in human male fertility and infertility.

scholarly journals Elevated expression of the Sertoli cell androgen receptor disrupts male fertility

2016 ◽  
Vol 311 (2) ◽  
pp. E396-E404 ◽  
Author(s):  
Rasmani Hazra ◽  
Dannielle Upton ◽  
Reena Desai ◽  
Omar Noori ◽  
Mark Jimenez ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Male Fertility ◽  
Leydig Cells ◽  
Cell Function ◽  
Pubertal Development ◽  
Receptor Expression ◽  
Testis Size

Recently, we created a unique gain-of-function mouse model with Sertoli cell-specific transgenic androgen receptor expression (TgSCAR) showing that SCAR activity controls the synchronized postnatal development of somatic Sertoli and Leydig cells and meiotic-postmeiotic germ cells. Moderate TgSCAR (TgSCARm) expression reduced testis size but had no effect on male fertility. Here, we reveal that higher TgSCAR expression (TgSCARH) causes male infertility. Higher SCAR activity, shown by upregulated AR-dependent transcripts ( Rhox5, Spinw1), resulted in smaller adult TgSCARH testes (50% of normal) despite normal or elevated circulating and intratesticular testosterone levels. Unlike fertile TgSCARm males, testes of adult TgSCARH males exhibited focal regions of interstitial hypertrophy featuring immature adult Leydig cells and higher intratesticular dihydrotestosterone and 5α-androstane 3α,17β-diol levels that are normally associated with pubertal development. Mature TgSCARH testes also exhibited markedly reduced Sertoli cell numbers (70%), although meiotic and postmeiotic germ cell/Sertoli cell ratios were twofold higher than normal, suggesting that elevated TgSCAR activity supports excessive spermatogenic development. Concurrent with the higher germ cell load of TgSCARH Sertoli cells were increased levels of apoptotic germ cells in TgSCARH relative to TgSCARm testes. In addition, TgSCARH testes displayed unique morphological degeneration that featured accumulated cellular and spermatozoa clusters in dilated channels of rete testes, consistent with reduced epididymal sperm numbers. Our findings reveal for the first time that excessive Sertoli cell AR activity in mature testes can reach a level that disturbs Sertoli/germ cell homeostasis, impacts focal Leydig cell function, reduces sperm output, and disrupts male fertility.

scholarly journals Essential role of CFAP53 in sperm flagellum biogenesis

2021 ◽  
Author(s):  
Bingbing Wu ◽  
Xiaochen Yu ◽  
Chao Liu ◽  
Lina Wang ◽  
Tao Huang ◽  
...  
Keyword(s):  
Male Fertility ◽  
Essential Role ◽  
Expression Level ◽  
Research Progress ◽  
Male Mice ◽  
Sperm Tail ◽  
Sperm Flagellum ◽  
Associated Proteins ◽  
Cilia And Flagella

AbstractThe sperm flagellum is essential for male fertility. Despite vigorous research progress towards understanding the pathogenesis of flagellum-related diseases, much remains unknown about the mechanisms underlying the flagellum biogenesis itself. Here, we show that the cilia and flagella associated protein 53 (Cfap53) gene is predominantly expressed in testes, and it is essential for sperm flagellum biogenesis. The knockout of this gene resulted in complete infertility in male mice but not in the females. CFAP53 localized to the manchette and sperm tail during spermiogenesis, the knockout of this gene impaired flagellum biogenesis. Furthermore, we identified two manchette and sperm tail-associated proteins that interacted with CFAP53 during spermiogenesis. The disruption of Cfap53 decreased the expression level of these two proteins and disrupted their localization in spermatids. Together, our results suggest that CFAP53 is an essential protein for sperm flagellum biogenesis, and its mutations might be associated with MMAF.

Genetic Control of Male Fertility in Higher Plants

1992 ◽  
Vol 19 (4) ◽  
pp. 419 ◽  
Author(s):  
AM Chaudhury ◽  
S Craig ◽  
KC Bloemer ◽  
L Farrell ◽  
ES Dennis
Keyword(s):  
Male Fertility ◽  
Higher Plants ◽  
Male Gamete ◽  
Genetic Dissection ◽  
Temporal Expression ◽  
Chromosome Walking ◽  
Male Sterile ◽  
Complex Process ◽  
Fertility Genes ◽  
Genome Manipulation

Male development in higher plants is a complex process which requires the correct spatial and temporal expression of a large number of male fertility genes. They include the genes required for the structure of the male organs, as well as genes required for male gamete development. Male-sterile mutants, impaired in male fertility functions, have helped to identify a number of these genes in various plant species including Arabidopsis thaliana, the model crucifer. In A. thaliana, once these genes are mapped, they can be cloned by chromosome walking. Alternative strategies of cloning will be facilitated by the isolation of similar mutants by tagging with transposable elements, T-DNA, or by mutagen-induced deletion. Once the genes required for male fertility are cloned and their wild type function identified, an understanding of the molecular basis of male fertility is likely to result. The combination of genetic dissection and the modern techniques of genome manipulation have made such a goal feasible.

MANAGEMENT MODELS OF DATA COLLECTION PROCESSES IN IOT NETWORKS WITH THE DYNAMIC STRUCTURE

2020 ◽  
Vol 7 (3) ◽  
pp. 62-71
Author(s):  
AUNG MYO THAW ◽  
◽  
ABBAS SADDAM AHMED ◽  
NATALIA ZHUKOVA ◽  
VLADIMIR CHERNOKULSKY ◽  
...  
Keyword(s):  
Energy Efficiency ◽  
Data Collection ◽  
Dynamic Networks ◽  
Dynamic Structure ◽  
Management Models ◽  
Complex Process ◽  
Management Processes

The collection of data from the network with dynamic structure is a complex process that must be performed with considering of security, energy efficiency and latency requirements. To determine the optimal data collection models that meet the stated requirements, the authors analyzed models and methods of data collection in dynamic networks, as well as management processes of data collection. The study allows to determine the most effective technologies for data collection in dynamic networks, which include Fog technologies and clustering technologies. Based on the analysis, the authors have developed the model for data collection managment, which allows to construct and rebuild the structures of data collection models in accordance with the requirements and conditions of data collection. The developed approaches and principles were successfully implemented in practice: a system of data collection was tested for the crane complexes, which is designed to work at production sites. In general, the study allows to identify methods and tools that effectively solve the problems of data collection in the networks with dynamic structure, and to demonstrate the solution of these problems in practice.

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