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Gut Jan 2021
Topics: Alginates; Animals; Fecal Microbiota Transplantation; Male; Mice; Oligosaccharides; Sperm Count; Sperm Motility; Spermatogenesis
PubMed: 32303608
DOI: 10.1136/gutjnl-2020-320992 -
Theranostics 2020: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug...
: Busulfan is currently an indispensable anti-cancer drug, particularly for children, but the side effects on male reproduction are so serious that critical drug management is needed to minimize any negative impact. Meanwhile, alginate oligosaccharides (AOS) are natural products with many consequent advantages, that have attracted a great deal of pharmaceutical attention. In the current investigation, we performed single-cell RNA sequencing on murine testes treated with busulfan and/or AOS to define the mitigating effects of AOS on spermatogenesis at the single cell level. : Testicular cells () were examined by single cell RNA sequencing analysis, histopathological analysis, immunofluorescence staining, and Western blotting. Testes samples () underwent RNA sequencing analysis. Blood and testicular metabolomes were determined by liquid chromatography-mass spectrometry (LC/MS). : We found that AOS increased murine sperm concentration and motility, and rescued busulfan disrupted spermatogenesis through improving (i) the proportion of germ cells, (ii) gene expression important for spermatogenesis, and (iii) transcriptional factors . Furthermore, AOS promoted the expression of genes important for spermatogenesis Finally, our results showed that AOS improved blood and testis metabolomes as well as the gut microbiota to support the recovery of spermatogenesis. : AOS could be used to improve fertility in patients undergoing chemotherapy and to combat other factors that induce infertility in humans.
Topics: Alginates; Animals; Blood; Busulfan; Cellular Microenvironment; Drug Evaluation, Preclinical; Gastrointestinal Microbiome; Infertility, Male; Male; Metabolome; Mice; Mice, Inbred ICR; Oligosaccharides; Protein Interaction Mapping; RNA-Seq; Single-Cell Analysis; Sperm Motility; Spermatogenesis; Testis; Transcriptome
PubMed: 32194870
DOI: 10.7150/thno.43189 -
Nature Communications Sep 2021Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight...
Molecular mechanisms associated with human germ cell aplasia in infertile men remain undefined. Here we perform single-cell transcriptome profiling to highlight differentially expressed genes and pathways in each somatic cell type in testes of men with idiopathic germ cell aplasia. We identify immaturity of Leydig cells, chronic tissue inflammation, fibrosis, and senescence phenotype of the somatic cells, as well markers of chronic inflammation in the blood. We find that deregulated expression of parentally imprinted genes in myoid and immature Leydig cells, with relevant changes in the ratio of Lamin A/C transcripts and an active DNA damage response in Leydig and peritubular myoid cells are also indicative of senescence of the testicular niche. This study offers molecular insights into the pathogenesis of idiopathic germ cell aplasia.
Topics: Aging; Cell Communication; Chemokines; DNA Damage; Gene Expression Profiling; Germ Cells; Humans; Inflammation; Leydig Cells; Male; Phenotype; Sequence Alignment; Spermatogenesis; Spermatogonia; Testis; Transcriptome
PubMed: 34471128
DOI: 10.1038/s41467-021-25544-0 -
Frontiers in Endocrinology 2022
Topics: Humans; Male; Spermatogenesis; Testis
PubMed: 35957828
DOI: 10.3389/fendo.2022.984409 -
Philosophical Transactions of the Royal... May 2010The role of oestrogens in male reproductive tract physiology has for a long time been a subject of debate. The testis produces significant amounts of oestrogenic... (Review)
Review
The role of oestrogens in male reproductive tract physiology has for a long time been a subject of debate. The testis produces significant amounts of oestrogenic hormones, via aromatase, and oestrogen receptors (ERs)alpha (ESR1) and ERbeta (ESR2) are selectively expressed in cells of the testis as well as the epididymal epithelium, depending upon species. This review summarizes the current knowledge concerning the presence and activity of aromatase and ERs in testis and sperm and the potential roles that oestrogens may have in mammalian spermatogenesis. Data show that physiology of the male gonad is in part under the control of a balance of androgens and oestrogens, with aromatase serving as a modulator.
Topics: Animals; Estrogens; Humans; Male; Spermatogenesis; Spermatozoa; Testis
PubMed: 20403867
DOI: 10.1098/rstb.2009.0235 -
Biology of Reproduction Jul 2018Spermatogonial stem cells (SSCs) are the most primitive spermatogonia in the testis and have an essential role to maintain highly productive spermatogenesis by... (Review)
Review
Spermatogonial stem cells (SSCs) are the most primitive spermatogonia in the testis and have an essential role to maintain highly productive spermatogenesis by self-renewal and continuous generation of daughter spermatogonia that differentiate into spermatozoa, transmitting genetic information to the next generation. Since the 1950s, many experimental methods, including histology, immunostaining, whole-mount analyses, and pulse-chase labeling, had been used in attempts to identify SSCs, but without success. In 1994, a spermatogonial transplantation method was reported that established a quantitative functional assay to identify SSCs by evaluating their ability to both self-renew and differentiate to spermatozoa. The system was originally developed using mice and subsequently extended to nonrodents, including domestic animals and humans. Availability of the functional assay for SSCs has made it possible to develop culture systems for their ex vivo expansion, which dramatically advanced germ cell biology and allowed medical and agricultural applications. In coming years, SSCs will be increasingly used to understand their regulation, as well as in germline modification, including gene correction, enhancement of male fertility, and conversion of somatic cells to biologically competent male germline cells.
Topics: Adult Germline Stem Cells; Animals; Humans; Male; Spermatogenesis; Spermatogonia; Testis
PubMed: 29617903
DOI: 10.1093/biolre/ioy077 -
Annual Review of Genetics Nov 2022Spermatogenesis is a complex differentiation process coordinated spatiotemporally across and along seminiferous tubules. Cellular heterogeneity has made it challenging... (Review)
Review
Spermatogenesis is a complex differentiation process coordinated spatiotemporally across and along seminiferous tubules. Cellular heterogeneity has made it challenging to obtain stage-specific molecular profiles of germ and somatic cells using bulk transcriptomic analyses. This has limited our ability to understand regulation of spermatogenesis and to integrate knowledge from model organisms to humans. The recent advancement of single-cell RNA-sequencing (scRNA-seq) technologies provides insights into the cell type diversity and molecular signatures in the testis. Fine-grained cell atlases of the testis contain both known and novel cell types and define the functional states along the germ cell developmental trajectory in many species. These atlases provide a reference system for integrated interspecies comparisons to discover mechanistic parallels and to enable future studies. Despite recent advances, we currently lack high-resolution data to probe germ cell-somatic cell interactions in the tissue environment, but the use of highly multiplexed spatial analysis technologies has begun to resolve this problem. Taken together, recent single-cell studies provide an improvedunderstanding of gametogenesis to examine underlying causes of infertility and enable the development of new therapeutic interventions.
Topics: Humans; Male; Transcriptome; Spermatogenesis; Testis; Gene Expression Profiling; Cell Differentiation
PubMed: 36070560
DOI: 10.1146/annurev-genet-080320-040045 -
Seminars in Cell & Developmental Biology Jan 2022Male fertility requires the continual production of sperm by the process of spermatogenesis. This process requires the correct timing of regulatory signals to germ cells... (Review)
Review
Male fertility requires the continual production of sperm by the process of spermatogenesis. This process requires the correct timing of regulatory signals to germ cells during each phase of their development. MicroRNAs (miRNAs) in germ cells and supporting Sertoli cells respond to regulatory signals and cause down- or upregulation of mRNAs and proteins required to produce proteins that act in various pathways to support spermatogenesis. The targets and functional consequences of altered miRNA expression in undifferentiated and differentiating spermatogonia, spermatocytes, spermatids and Sertoli cells are discussed. Mechanisms are reviewed by which miRNAs contribute to decisions that promote spermatogonia stem cell self-renewal versus differentiation, entry into and progression through meiosis, differentiation of spermatids, as well as the regulation of Sertoli cell proliferation and differentiation. Also discussed are miRNA actions providing the very first signals for the differentiation of spermatogonia stem cells in a non-human primate model of puberty initiation.
Topics: Animals; Humans; Male; MicroRNAs; Spermatogenesis
PubMed: 34006455
DOI: 10.1016/j.semcdb.2021.05.009 -
Journal of Cell Science Jul 2020Mitochondrial fusion and fission (mitochondrial dynamics) are homeostatic processes that safeguard normal cellular function. This relationship is especially strong in... (Review)
Review
Mitochondrial fusion and fission (mitochondrial dynamics) are homeostatic processes that safeguard normal cellular function. This relationship is especially strong in tissues with constitutively high energy demands, such as brain, heart and skeletal muscle. Less is known about the role of mitochondrial dynamics in developmental systems that involve changes in metabolic function. One such system is spermatogenesis. The first mitochondrial dynamics gene, (), was discovered in 1997 to mediate mitochondrial fusion during spermatogenesis. In mammals, however, the role of mitochondrial fusion during spermatogenesis remained unknown for nearly two decades after discovery of Mammalian spermatogenesis is one of the most complex and lengthy differentiation processes in biology, transforming spermatogonial stem cells into highly specialized sperm cells over a 5-week period. This elaborate differentiation process requires several developmentally regulated mitochondrial and metabolic transitions, making it an attractive model system for studying mitochondrial dynamics We review the emerging role of mitochondrial biology, and especially its dynamics, during the development of the male germ line.
Topics: Animals; Drosophila; Drosophila Proteins; Male; Mitochondria; Mitochondrial Dynamics; Spermatogenesis
PubMed: 32675215
DOI: 10.1242/jcs.235937 -
Cells & Development Sep 2023The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies, sperm phenotypes, and the process of... (Review)
Review
The testis is a key male reproductive organ that produces gametes through the process of spermatogenesis. Testis morphologies, sperm phenotypes, and the process of spermatogenesis evolve rapidly in mammals, presumably due to the evolutionary pressure on males to give rise to their own offspring. Here, we review studies illuminating the molecular evolution of the testis, in particular large-scale transcriptomic studies, which were based on bulk tissue samples and, more recently, individual cells. Together with various genomic and epigenomic data, these studies have unveiled the cellular source, molecular mechanisms, and evolutionary forces that underlie the rapid phenotypic evolution of the testis. They also revealed shared (ancestral) and species-specific spermatogenic gene expression programs. The insights and available data that have accumulated also provide a valuable resource for the investigation and treatment of male fertility disorders - a dramatically increasing problem in modern industrial societies.
Topics: Animals; Male; Semen; Spermatogenesis; Testis; Evolution, Molecular; Mammals
PubMed: 37336426
DOI: 10.1016/j.cdev.2023.203865