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Frontiers in Endocrinology 2022
Topics: Humans; Male; Spermatogenesis; Testis
PubMed: 35957828
DOI: 10.3389/fendo.2022.984409 -
Philosophical Transactions of the Royal... May 2010Different cellular events occur during spermatogenesis, and these include (i) mitosis for self-renewal of spermatogonia, (ii) differentiation of type A spermatogonia... (Review)
Review
Different cellular events occur during spermatogenesis, and these include (i) mitosis for self-renewal of spermatogonia, (ii) differentiation of type A spermatogonia into type B and commitment of type B spermatogonia to develop into preleptotene primary spermatocytes, (iii) transit of preleptotene/leptotene spermatocytes across the blood-testis barrier in coordination with germ cell cycle progression and meiosis, (iv) spermiogenesis and spermiation. These events also associate with extensive changes in cell shape and size, and germ cell movement. The cytoskeleton, which comprises actin, microtubules and intermediate filaments, is believed to function in these cellular events. However, few studies have been conducted by investigators in the past decades to unfold the role of the cytoskeleton during spermatogenesis. This review summarizes recent advances in the field relating to cytoskeletal dynamics in the testis, and highlights areas of research that require additional emphasis so that new approaches for male contraception, as well as therapeutic approaches to alleviate environmental toxicant-induced reproductive dysfunction in men, can possibly be developed.
Topics: Cell Communication; Cytoskeletal Proteins; Cytoskeleton; Humans; Male; Seminiferous Epithelium; Sertoli Cells; Spermatogenesis; Spermatozoa
PubMed: 20403871
DOI: 10.1098/rstb.2009.0261 -
Development (Cambridge, England) Nov 2023Sperm flagellum plays a crucial role in male fertility. Here, we generated Ccdc183 knockout mice using the CRISPR/Cas9 system to reveal the protein function of the...
Sperm flagellum plays a crucial role in male fertility. Here, we generated Ccdc183 knockout mice using the CRISPR/Cas9 system to reveal the protein function of the testis-specific protein CCDC183 in spermiogenesis. We demonstrated that the absence of CCDC183 causes male infertility with morphological and motility defects in spermatozoa. Owing to the lack of CCDC183, centrioles after elongation of axonemal microtubules do not connect the cell surface and nucleus during spermiogenesis, which causes subsequent loss of cytoplasmic invagination around the flagellum. As a result, the flagellar compartment does not form properly and cytosol-exposed axonemal microtubules collapse during spermiogenesis. In addition, ectopic localization of accessory structures, such as the fibrous sheath and outer dense fibers, and abnormal head shape as a result of abnormal sculpting by the manchette are observed in Ccdc183 knockout spermatids. Our results indicate that CCDC183 plays an essential role in cytoplasmic invagination around the flagellum to form functional spermatozoa during spermiogenesis.
Topics: Mice; Animals; Male; Cytosol; Semen; Spermatogenesis; Flagella; Mice, Knockout; Fertility
PubMed: 37882665
DOI: 10.1242/dev.201724 -
Toxicological Sciences : An Official... Oct 2020Studies have shown that mammalian testes, in particular the Sertoli cells, are highly susceptible to exposure of environmental toxicants, such as cadmium,... (Review)
Review
Studies have shown that mammalian testes, in particular the Sertoli cells, are highly susceptible to exposure of environmental toxicants, such as cadmium, perfluorooctanesulfonate, phthalates, 2,5-hexanedione and bisphenol A. However, important studies conducted by reproductive toxicologists and/or biologists in the past have been treated as toxicology reports per se. Yet, many of these studies provided important mechanistic insights on the toxicant-induced testis injury and reproductive dysfunction, relevant to the biology of the testis and spermatogenesis. Furthermore, recent studies have shown that findings obtained from toxicant models are exceedingly helpful tools to unravel the biology of testis function in particular spermatogenesis, including specific cellular events associated with spermatid transport to support spermiogenesis and spermiation. In this review, we critically evaluate some recent data, focusing primarily on the molecular structure and role of microtubules in cellular function, illustrating the importance of toxicant models to unravel the biology of microtubule cytoskeleton in supporting spermatogenesis, well beyond information on toxicology. These findings have opened up some potential areas of research which should be carefully evaluated in the years to come.
Topics: Animals; Cytoskeleton; Hazardous Substances; Male; Microtubules; Sertoli Cells; Spermatogenesis; Testis
PubMed: 32647867
DOI: 10.1093/toxsci/kfaa109 -
International Journal of Molecular... Feb 2022Maturing male germ cells undergo a unique developmental process in spermiogenesis that replaces nucleosomal histones with protamines, the process of which is critical...
Maturing male germ cells undergo a unique developmental process in spermiogenesis that replaces nucleosomal histones with protamines, the process of which is critical for testicular development and male fertility. The progress of this exchange is regulated by complex mechanisms that are not well understood. Now, with mouse genetic models, we show that barrier-to-autointegration factor-like protein (BAF-L) plays an important role in spermiogenesis and spermatozoal function. BAF-L is a male germ cell marker, whose expression is highly associated with the maturation of male germ cells. The genetic deletion of BAF-L in mice impairs the progress of spermiogenesis and thus male fertility. This effect on male fertility is a consequence of the disturbed homeostasis of histones and protamines in maturing male germ cells, in which the interactions between BAF-L and histones/protamines are implicated. Finally, we show that reduced testicular expression of BAF-L represents a risk factor of human male infertility.
Topics: Animals; Biomarkers; Gene Expression Regulation, Developmental; Germ Cells; Histones; Humans; Infertility, Male; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nuclear Proteins; Protamines; Spermatids; Spermatogenesis; Testis
PubMed: 35216101
DOI: 10.3390/ijms23041985 -
ELife Oct 2021The mammalian Y chromosome is critical for male sex determination and spermatogenesis. However, linking each Y gene to specific aspects of male reproduction has been... (Review)
Review
The mammalian Y chromosome is critical for male sex determination and spermatogenesis. However, linking each Y gene to specific aspects of male reproduction has been challenging. As the Y chromosome is notoriously hard to sequence and target, functional studies have mostly relied on transgene-rescue approaches using mouse models with large multi-gene deletions. These experimental limitations have oriented the field toward the search for a minimum set of Y genes necessary for male reproduction. Here, considering Y-chromosome evolutionary history and decades of discoveries, we review the current state of research on its function in spermatogenesis and reassess the view that many Y genes are disposable for male reproduction.
Topics: Animals; Biological Evolution; Humans; Male; Mammals; Mice; Spermatogenesis; Y Chromosome
PubMed: 34606444
DOI: 10.7554/eLife.67345 -
Andrology Jul 2020The germline serves as a conduit for transmission of genetic and epigenetic information from one generation to the next. In males, spermatozoa are the final carriers of... (Review)
Review
BACKGROUND
The germline serves as a conduit for transmission of genetic and epigenetic information from one generation to the next. In males, spermatozoa are the final carriers of inheritance and their continual production is supported by a foundational population of spermatogonial stem cells (SSCs) that forms from prospermatogonial precursors during the early stages of neonatal development. In mammals, the timing for which SSCs are specified and the underlying mechanisms guiding this process remain to be completely understood.
OBJECTIVES
To propose an evolving concept for how the foundational SSC population is established.
MATERIALS AND METHODS
This review summarizes recent and historical findings from peer-reviewed publications made primarily with mouse models while incorporating limited studies from humans and livestock.
RESULTS AND CONCLUSION
Establishment of the SSC population appears to follow a biphasic pattern involving a period of fate programming followed by an establishment phase that culminates in formation of the SSC population. This model for establishment of the foundational SSC population from precursors is anticipated to extend across mammalian species and include humans and livestock, albeit on different timescales.
Topics: Adult Germline Stem Cells; Animals; Cattle; Humans; Male; Mice; Spermatogenesis; Spermatogonia
PubMed: 32356598
DOI: 10.1111/andr.12810 -
Seminars in Cell & Developmental Biology Nov 2016When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are... (Review)
Review
When the cross-section of a seminiferous tubule from an adult rat testes is examined microscopically, Sertoli cells and germ cells in the seminiferous epithelium are notably polarized cells. For instance, Sertoli cell nuclei are found near the basement membrane. On the other hand, tight junction (TJ), basal ectoplasmic specialization (basal ES, a testis-specific actin-rich anchoring junction), gap junction (GJ) and desmosome that constitute the blood-testis barrier (BTB) are also located near the basement membrane. The BTB, in turn, divides the epithelium into the basal and the adluminal (apical) compartments. Within the epithelium, undifferentiated spermatogonia and preleptotene spermatocytes restrictively reside in the basal compartment whereas spermatocytes and post-meiotic spermatids reside in the adluminal compartment. Furthermore, the heads of elongating/elongated spermatids point toward the basement membrane with their elongating tails toward the tubule lumen. However, the involvement of polarity proteins in this unique cellular organization, in particular the underlying molecular mechanism(s) by which polarity proteins confer cellular polarity in the seminiferous epithelium is virtually unknown until recent years. Herein, we discuss latest findings regarding the role of different polarity protein complexes or modules and how these protein complexes are working in concert to modulate Sertoli cell and spermatid polarity. These findings also illustrate polarity proteins exert their effects through the actin-based cytoskeleton mediated by actin binding and regulatory proteins, which in turn modulate adhesion protein complexes at the cell-cell interface since TJ, basal ES and GJ utilize F-actin for attachment. We also propose a hypothetical model which illustrates the antagonistic effects of these polarity proteins. This in turn provides a unique mechanism to modulate junction remodeling in the testis to support germ cell transport across the epithelium in particular the BTB during the epithelial cycle of spermatogenesis.
Topics: Animals; Cell Polarity; Cytoskeleton; Humans; Models, Biological; Protein Binding; Proteins; Spermatogenesis
PubMed: 27292315
DOI: 10.1016/j.semcdb.2016.06.008 -
Biochimica Et Biophysica Acta Mar 2014The function of sperm is to safely transport the haploid paternal genome to the egg containing the maternal genome. The subsequent fertilization leads to transmission of... (Review)
Review
The function of sperm is to safely transport the haploid paternal genome to the egg containing the maternal genome. The subsequent fertilization leads to transmission of a new unique diploid genome to the next generation. Before the sperm can set out on its adventurous journey, remarkable arrangements need to be made during the post-meiotic stages of spermatogenesis. Haploid spermatids undergo extensive morphological changes, including a striking reorganization and compaction of their chromatin. Thereby, the nucleosomal, histone-based structure is nearly completely substituted by a protamine-based structure. This replacement is likely facilitated by incorporation of histone variants, post-translational histone modifications, chromatin-remodeling complexes, as well as transient DNA strand breaks. The consequences of mutations have revealed that a protamine-based chromatin is essential for fertility in mice but not in Drosophila. Nevertheless, loss of protamines in Drosophila increases the sensitivity to X-rays and thus supports the hypothesis that protamines are necessary to protect the paternal genome. Pharmaceutical approaches have provided the first mechanistic insights and have shown that hyperacetylation of histones just before their displacement is vital for progress in chromatin reorganization but is clearly not the sole inducer. In this review, we highlight the current knowledge on post-meiotic chromatin reorganization and reveal for the first time intriguing parallels in this process in Drosophila and mammals. We conclude with a model that illustrates the possible mechanisms that lead from a histone-based chromatin to a mainly protamine-based structure during spermatid differentiation. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development.
Topics: Animals; Chromatin Assembly and Disassembly; DNA Breaks; Drosophila melanogaster; Genomic Instability; Histones; Humans; Male; Mice; Nucleosomes; Protein Processing, Post-Translational; Spermatids; Spermatogenesis
PubMed: 24091090
DOI: 10.1016/j.bbagrm.2013.08.004 -
Reproduction (Cambridge, England) Nov 2015Spermatogenesis is a complex and tightly regulated process leading to the continuous production of male gametes, the spermatozoa. This developmental process requires the... (Review)
Review
Spermatogenesis is a complex and tightly regulated process leading to the continuous production of male gametes, the spermatozoa. This developmental process requires the sequential and coordinated expression of thousands of genes, including many that are testis-specific. The molecular networks underlying normal and pathological spermatogenesis have been widely investigated in recent decades, and many high-throughput expression studies have studied genes and proteins involved in male fertility. In this review, we focus on studies that have attempted to correlate transcription and translation during spermatogenesis by comparing the testicular transcriptome and proteome. We also discuss the recent development and use of new transcriptomic approaches that provide a better proxy for the proteome, from both qualitative and quantitative perspectives. Finally, we provide illustrations of how testis-derived transcriptomic and proteomic data can be integrated to address new questions and how the 'proteomics informed by transcriptomics' technique, by combining RNA-seq and MS-based proteomics, can contribute significantly to the discovery of new protein-coding genes or new protein isoforms expressed during spermatogenesis.
Topics: Animals; Gene Expression Regulation; Humans; Male; Proteome; Proteomics; Spermatogenesis; Transcriptome
PubMed: 26416010
DOI: 10.1530/REP-15-0073