Special Issue "Molecular Mechanism of Ciliogenesis/Spermatogenesis"
Deadline for manuscript submissions: 30 September 2021.
Interests: manchette; intraflagellar transport; transcriptional regulation; acrosome biogenesis
Interests: genetics of male infertility; asthenozoospermia; ciliopathy
Spermatogenesis is a highly specialized physiological process during which male germ cells proliferate, undergo meiosis and differentiate to produce spermatozoa. During this process, germ cells undergo major morphological modifications, including acrosome formation, chromosome condensation and flagellogenesis. The acrosome is a cap-like structure mainly derived from the Golgi apparatus. It contains digestive enzymes that break down the outer membrane of the ovum for normal fertilization. Of the morphological modifications, flagellum formation is the most spectacular. The sperm flagellum acts as a propulsive organelle that allows the sperm cells to reach and penetrate the egg at fertilization. This motility is generated by a microtubule-based cytoskeletal structure that forms the core of the flagellum, called the axoneme. The axonemal structure consists of nine outer double microtubules surrounding a central pair of single microtubules. This structure that has been well conserved through evolution and is also present in cilia on the trachea, oviducts and numerous other tissues. In addition to the axoneme, sperm flagellum comprises additional peri-axonemal structures, allowing this organelle to function differently. Two major transport systems, the intra-manchette transport and intraflagellar transport, are believed to play essentiaol roles in transporting cargo proteins for normal sperm flagella formation. Male germ cells have unique regularatory mechanisms for gene expression, including transcriptional and epigenetic regulation such as DNA methylation. Non-coding RNAs including piRNAs play important roles in normal germ cell development. Defects in these germ cell-specific structures are responsible of asthenozoospermia and male infertility that could be isolated or associated with ciliopathy. Recent advances in both techniques of high throughput sequencing (HTS) and genome editing have facilitated the increase of our fundamental and clinical knowledge about the function of numerous genes implicated in these disorders. For example, the use of whole exome sequencing these last years led to the discovery of more than 20 genes responsible for multiples morphological abnormalities in sperm flagella (MMAF syndrome), and more than 40 genes have been reported in primary ciliary dyskinesia (PCD). The CRISPR/Cas9 is a complementary technique to HTS that accelerates the production of transgenic animal models to validate the pathogenic effect of the identified variants and to study the function of genes of interest. The main aim of this topic is to elucidate the high complexity of the molecular network underlying the structural organisation and function of such organelles and to explore the molecular pathogeny associated with their disorders which lead to male infertility and/or ciliopathies.
Dr. Zhibing Zhang
Dr. Zine Eddine Kherraf
Prof. Shuiqiao Yuan
Manuscript Submission Information
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- Acrosome biogenesis
- Intraflagellar transport
- Transcriptional regulation
- DNA methylation
- Genetics of male infertility
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Aging-induced changes in sperm sncRNA in rat are modified by low dose of perinatal flame retardants
Authors: Alexander Suvorov
Affiliation: Institute of Experimental Medicine of the North-West Branch of the Russian Academy of Medical Sciences, Saint Petersburg (ex Leningrad), Russian Federation
Abstract: Advanced paternal age at fertilization is a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental and life-style factors that modify such changes. In this study, we characterize age-dependent changes in sperm profiles of sncRNA between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). Small RNA libraries were prepared from caudal epididymal sperm sequenced with an average 16.5 million reads per sample and differentially expressed sncRNA were identified using DESeq 2. Distribution of small RNA fractions changed with age, with fractions of reads mapping to rRNA and lncRNA decreasing and fractions of reads mapping to tRNA and miRNA increasing. Furthermore, we identified 249 miRNA, 908 piRNA and 227 tRNA-derived RNA significantly differentially expressed (2 fold change, FDR adjusted p ≤ 0.05) between age groups in control animals. Differentially expressed miRNA and piRNA were enriched for protein-coding targets involved in development and metabolism. Additionally, piRNA were enriched for LTR targets. Exposure to BDE-47 had only minor effect on expression of sncRNA as compared between exposed and control groups within age groups. However, exposure had significantly modified the effect of aging, likely due to increased variance in expression of all sncRNA and attenuated effect of age on miRNA expression. In conclusion, our results indicate that the natural aging process has profound effects on sperm sncRNA and this effect may be modified by environmental exposures. Moreover, our results further support the role of sncRNA as a biomarker and likely mechanism by which advanced paternal age is associated with adverse offspring health and development.
Title: AKAP3-associated sperm flagellar malformation
Authors: Feng Zhang
Abstract: AKAP3-associated sperm flagellar malformation
Title: Protein kinase A-mediated septin7 phosphorylation disrupts septin filaments and ciliogenesis
Authors: Han-Yu Wang; Chun-Hsiang Lin; Yi-Ru Shen; Ting-Yu Chen; Chia-Yih Wang; Pao-Lin Kuo
Affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University
Abstract: Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among these septins, septin7 (SEPT7) is an important component of all septin filaments. Here we showed that protein kinase A (PKA) phosphorylates SEPT7 at Thr197 thus disrupting septin filament dynamics and ciliogenesis. Thr197 residue of SEPT7, a PKA phosphorylating site, was conserved among different species. Treatment of cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation followed by disrupting septin filament formation. Constitutive phosphorylation of SEPT7 at Thr197 reduced SEPT7-SEPT7 interaction, but not affected SEPT7-SEPT6-SEPT2 or SEPT4 interaction. Besides, we also identified SEPT7 interacted with the PKACA2 via its GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.
Title: Impact of age on spermatogenic function and sperm parameters in tomcats (Felis catus)
Affiliation: Department of Veterinary Sciences Faculty of Agrobiology, Food and Natural Resources Czech University of Life Sciences Prague
Abstract: This study aims to provide a comprehensive assessment of reproductive function in sexually mature cats of two different ages. Tomcats are considered sexually mature around 1 year of age despite most of them showing complete spermatogenesis and epididymal sperm reserve when they are 7 months old. Sixteen tomcats were used and classified according to their age as young (<1 year old) or adult (˃1 year old). All tomcats were sexually mature based on the presence of complete spermatogenesis and spermatozoa in their epididymal caudae. Testicular and epididymal mass, spermatogenic indexes, and sperm parameters (kinetics, morphometry, DNA integrity, mitochondrial activity, etc.) are evaluated. Special emphasis is given to the relationships between Sertoli cell function and sperm size.
Title: The transformation of the centrosome into the basal body – Similarities and dissimilarities between somatic and germ cells
Authors: Sigrid Hoyer-Fender
Affiliation: Georg-August University of Göttingen, Göttingen Center of Molecular Biosciences, Jo-hann-Friedrich-Blumenbach Institute for Zoology and Anthropology-Developmental Biology, Ernst-Caspari-Haus, Göttingen.
Abstract: The flagellum of the sperm is essential for the transport of the genetic material towards the oocyte and thus the transmission of the genetic information to the next generation. During the haploid phase of spermatogenesis, i.e. spermiogenesis, a morphological and molecular restructuring of the male germ cell, the round spermatid, takes place that includes the silencing and compaction of the nucleus, the formation of the acrosomic vesicle from the Golgi apparatus, the formation of the sperm tail, and, fi-nally, the shedding of excessive cytoplasm. Formation of the sperm tail starts in the round spermatid stage, when the pair of centrioles moves towards the posterior pole of the nucleus The sperm tail, thus, becomes located opposed to the acrosomic vesicle, which develops at the anterior pole of the nucleus. The centriolar pair tightly attaches to the nucleus, forming a nuclear membrane indentation. Around the centriolar pair a sophisticated structure is formed known as the connecting piece, which forms the neck region, linking the sperm head to the tail, also named the head to tail coupling apparatus or, in short, HTCA. Finally, the sperm tail grows out from the distal centriole of the centriolar pair that is now transformed into the basal body of the flagellum. However, a centriolar pair is found in nearly all cells of the body. In somatic cells, it accumulates a large mass of proteins, the pericentriolar material (PCM), that both together constitutes the centrosome that is the main microtubule organizing center of the cell, essential not only for the structuring of the cytoskeleton and the overall cellular organization, but also for mitotic spindle formation and chromosome segregation. However, in quiescent cells, which have exited the cell cycle, the centrosome is transformed into the basal body. In this case, one of the centrioles, which is always the oldest or mother centriole, grows the axoneme of a cilium. Nearly all cells of the body carry a single cilium known as the primary cilium. Besides that specialized cells develop a multitude of cilia on their surface that are motile, and are essential to move fluids or cargos over the cellular surface. Impairment of cilia formation causes numerous and severe syndromes that are collec-tively subsumed as ciliopathies. This comparative overview serves to elucidate the molecular mecha-nisms of basal body formation, their similiarities and dissimilarities, in somatic and germ cells, by dis-cussing the involved proteins/genes and their expression, localization, and function as inferred from model organisms. The review, thus, aimed to provide a deeper knowledge of the molecular players that is essential for expansion of clinical diagnostics and treatment of male fertility disorders.
Title: Evaluation of protein expression of testicular isoform of ACE in human sperm form infertile men in relation to capacitation and acrosome reaction
Authors: Nina Atanassova
Affiliation: Medical University - Plovdiv and Bulgarian Academy of Sciences.