-
Reproduction (Cambridge, England) Aug 2016Within the seminiferous tubules there are two major cell types, namely male germ cells and Sertoli cells. Recent studies have demonstrated that male germ cells and... (Review)
Review
Within the seminiferous tubules there are two major cell types, namely male germ cells and Sertoli cells. Recent studies have demonstrated that male germ cells and Sertoli cells can have significant applications in treating male infertility and other diseases. However, primary male germ cells are hard to proliferate in vitro and the number of spermatogonial stem cells is scarce. Therefore, methods that promote the expansion of these cell populations are essential for their use from the bench to the bed side. Notably, a number of cell lines for rodent spermatogonia, spermatocytes and Sertoli cells have been developed, and significantly we have successfully established a human spermatogonial stem cell line with an unlimited proliferation potential and no tumor formation. This newly developed cell line could provide an abundant source of cells for uncovering molecular mechanisms underlying human spermatogenesis and for their utilization in the field of reproductive and regenerative medicine. In this review, we discuss the methods for establishing spermatogonial, spermatocyte and Sertoli cell lines using various kinds of approaches, including spontaneity, transgenic animals with oncogenes, simian virus 40 (SV40) large T antigen, the gene coding for a temperature-sensitive mutant of p53, telomerase reverse gene (Tert), and the specific promoter-based selection strategy. We further highlight the essential applications of these cell lines in basic research and translation medicine.
Topics: Animals; Germ Cells; Humans; Infertility, Male; Male; Sertoli Cells; Spermatogenesis; Stem Cells
PubMed: 27069011
DOI: 10.1530/REP-15-0546 -
PloS One 2023Sertoli cells support the development of sperm and the function of various somatic cells in the interstitium between the tubules. Sertoli cells regulate the function of...
Sertoli cells support the development of sperm and the function of various somatic cells in the interstitium between the tubules. Sertoli cells regulate the function of the testicular vasculature and the development and function of the Leydig cells that produce testosterone for fertility and virility. However, the Sertoli cell-derived factors that regulate these cells are largely unknown. To define potential mechanisms by which Sertoli cells could support testicular somatic cell function, we aimed to identify Sertoli cell-enriched proteins in the testicular interstitial fluid (TIF) between the tubules. We previously resolved the proteome of TIF in mice and humans and have shown it to be a rich source of seminiferous tubule-derived proteins. In the current study, we designed bioinformatic strategies to interrogate relevant proteomic and genomic datasets to identify Sertoli cell-enriched proteins in mouse and human TIF. We analysed proteins in mouse TIF that were significantly reduced after one week of acute Sertoli cell ablation in vivo and validated which of these are likely to arise primarily from Sertoli cells based on relevant mouse testis RNASeq datasets. We used a different, but complementary, approach to identify Sertoli cell-enriched proteins in human TIF, taking advantage of high-quality human testis genomic, proteomic and immunohistochemical datasets. We identified a total of 47 and 40 Sertoli cell-enriched proteins in mouse and human TIF, respectively, including 15 proteins that are conserved in both species. Proteins with potential roles in angiogenesis, the regulation of Leydig cells or steroidogenesis, and immune cell regulation were identified. The data suggests that some of these proteins are secreted, but that Sertoli cells also deposit specific proteins into TIF via the release of extracellular vesicles. In conclusion, we have identified novel Sertoli cell-enriched proteins in TIF that are candidates for regulating somatic cell-cell communication and testis function.
Topics: Humans; Male; Animals; Mice; Sertoli Cells; Testis; Extracellular Fluid; Proteomics; Semen
PubMed: 37656709
DOI: 10.1371/journal.pone.0290846 -
Nature Aging May 2024
Topics: Humans; Male; Hypogonadism; Lysosomes; Sertoli Cells; Testosterone; Age of Onset
PubMed: 38671231
DOI: 10.1038/s43587-024-00622-2 -
FASEB Journal : Official Publication of... Mar 2024Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis...
Germ cell development depends on the capacity of somatic Sertoli cells to undergo differentiation into a mature state and establish a germ cell-specific blood-testis barrier (BTB). The BTB structure confers an immunological barrier for meiotic and postmeiotic germ cells, and its dynamic permeability facilitates a transient movement of preleptotene spermatocytes through BTB to enter meiosis. However, the regulatory factors involved in Sertoli cell maturation and how BTB dynamics coordinate germ cell development remain unclear. Here, we found a histone deacetylase HDAC3 abundantly expresses in Sertoli cells and localizes in both cytoplasm and nucleus. Sertoli cell-specific Hdac3 knockout in mice causes infertility with compromised integrity of blood-testis barrier, leading to germ cells unable to traverse through BTB and an accumulation of preleptotene spermatocytes in juvenile testis. Mechanistically, nuclear HDAC3 regulates the expression program of Sertoli cell maturation genes, and cytoplasmic HDAC3 forms a complex with the gap junction protein Connexin 43 to modulate the BTB integrity and dynamics through regulating the distribution of tight junction proteins. Our findings identify HDAC3 as a critical regulator in promoting Sertoli cell maturation and maintaining the homeostasis of the blood-testis barrier.
Topics: Animals; Male; Mice; Blood-Testis Barrier; Cell Differentiation; Sertoli Cells; Spermatocytes; Spermatogenesis; Testis; Tight Junctions; Histone Deacetylases
PubMed: 38430456
DOI: 10.1096/fj.202301349RR -
Seminars in Cell & Developmental Biology Sep 2018Cell polarity in the adult mammalian testis refers to the polarized alignment of developing spermatids during spermiogenesis and the polarized organization of organelles... (Review)
Review
Cell polarity in the adult mammalian testis refers to the polarized alignment of developing spermatids during spermiogenesis and the polarized organization of organelles (e.g., phagosomes, endocytic vesicles, Sertoli cell nuclei, Golgi apparatus) in Sertoli cells and germ cells to support spermatogenesis. Without these distinctive features of cell polarity in the seminiferous epithelium, it is not possible to support the daily production of millions of sperm in the limited space provided by the seminiferous tubules in either rodent or human males through the adulthood. In short, cell polarity provides a novel mean to align spermatids and the supporting organelles (e.g., phagosomes, Golgi apparatus, endocytic vesicles) in a highly organized fashion spatially in the seminiferous epithelium during the epithelial cycle of spermatogenesis. This is analogous to different assembling units in a manufacturing plant such that as developing spermatids move along the "assembly line" conferred by Sertoli cells, different structural/functional components can be added to (or removed from) the developing spermatids during spermiogenesis, so that functional spermatozoa are produced at the end of the assembly line. Herein, we briefly review findings regarding the regulation of cell polarity in the testis with specific emphasis on developing spermatids, supported by an intriguing network of regulatory proteins along a local functional axis. Emerging evidence has suggested that cell cytoskeletons provide the tracks which in turn confer the unique assembly lines in the seminiferous epithelium. We also provide some thought-provoking concepts based on which functional experiments can be designed in future studies.
Topics: Animals; Cell Polarity; Cytoskeleton; Humans; Male; Microtubules; Sertoli Cells; Spermatids; Spermatogenesis; Testis
PubMed: 28965865
DOI: 10.1016/j.semcdb.2017.09.037 -
Andrology Mar 2016It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed... (Review)
Review
It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.
Topics: Andrology; Animals; History, 19th Century; Humans; Male; Sertoli Cells
PubMed: 26846984
DOI: 10.1111/andr.12165 -
International Journal of Molecular... Jul 2016Aquaporins (AQPs) are proteinaceous channels widespread in nature where they allow facilitated permeation of water and uncharged through cellular membranes. AQPs play a... (Review)
Review
Aquaporins (AQPs) are proteinaceous channels widespread in nature where they allow facilitated permeation of water and uncharged through cellular membranes. AQPs play a number of important roles in both health and disease. This review focuses on the most recent advances and research trends regarding the expression and modulation, as well as physiological and pathophysiological functions of AQPs in hepatocytes and Sertoli cells (SCs). Besides their involvement in bile formation, hepatocyte AQPs are involved in maintaining energy balance acting in hepatic gluconeogenesis and lipid metabolism, and in critical processes such as ammonia detoxification and mitochondrial output of hydrogen peroxide. Roles are played in clinical disorders including fatty liver disease, diabetes, obesity, cholestasis, hepatic cirrhosis and hepatocarcinoma. In the seminiferous tubules, particularly in SCs, AQPs are also widely expressed and seem to be implicated in the various stages of spermatogenesis. Like in hepatocytes, AQPs may be involved in maintaining energy homeostasis in these cells and have a major role in the metabolic cooperation established in the testicular tissue. Altogether, this information represents the mainstay of current and future investigation in an expanding field.
Topics: Aquaporins; Energy Metabolism; Hepatocytes; Humans; Infertility, Male; Male; Mitochondria; Non-alcoholic Fatty Liver Disease; Reactive Oxygen Species; Sertoli Cells
PubMed: 27409609
DOI: 10.3390/ijms17071096 -
General and Comparative Endocrinology Mar 2019Neotropical icthyofauna represents one of the most diverse and extreme ecosystems in the world. Likewise, reproduction showed enormous diversity with different... (Review)
Review
Neotropical icthyofauna represents one of the most diverse and extreme ecosystems in the world. Likewise, reproduction showed enormous diversity with different reproductive systems, modes and behavior. On the other hand, information on Neotropical fish species, in particular on male reproductive physiology is restricted to few species. This mini-review aimed to compile the existing information on spermatogenesis of Neotropical teleosts focusing on testis structure, spermatogonial niche and Sertoli cell efficiency. The first topic covers the histological analysis of the testicular structure, showing a conserved testicular pattern in relation to the phylogenetic position: basal species present anastomosing tubular testis (e.g. Astyanax altiparanae, Conorhynchos conirostris, Pimelodus maculatus, Lophiosilurus alexandri, Rhinelepis aspera, among others), while derived teleosts showed lobular testis (e.g. Cichlasoma dimerus, Cichla kelberi, Odontesthes bonariensis, Synbranchus marmoratus and others). Next to testicular structure, existing data showed that type A undifferentiated spermatogonia (A) is differentially distributed among the Neotropical species. A can be restricted at the blind-end of the germinal compartment (O. bonariensis), or spread along the germinal epithelium (A. altiparanae), or even distributed along the germinal epithelium but concentrated at the blind-end (C. kelberi and C. intermedia). Moreover, recent studies in A. altiparanae have demonstrated that within the germinal compartment, A have a preferential distribution in areas neighboring the interstitial compartment - the spermatogonial niche. The proximity with the interstitium suggests that interstitial cells, such as Leydig cells, are important for A maintenance in the testis. Finally, this mini-review highlighted Sertoli cell efficiency, showing that a single Sertoli cell can support a higher number of germ cells (80-140 spermatids) in Neotropical species evaluated at the moment (e.g. A. altiparanae, Hoplias malabaricus, Poecilia reticulata, Serrasalmus spilopleura, C. intermedia). Overall, this review provided basic and functional information on spermatogenesis of Neotropical species. More studies in this field are necessary since Neotropical region is considered one of the hotspot regions to discovery new species providing, therefore, new opportunities to investigate spermatogenesis in fish.
Topics: Animals; Fishes; Male; Phylogeny; Sertoli Cells; Spermatogenesis; Spermatogonia; Testis
PubMed: 30195025
DOI: 10.1016/j.ygcen.2018.09.004 -
Endocrinology Oct 2022Microtubule affinity-regulating kinases (MARKs) are nonreceptor Ser/Thr protein kinases known to regulate cell polarity and microtubule dynamics in Caenorhabditis...
Microtubule affinity-regulating kinases (MARKs) are nonreceptor Ser/Thr protein kinases known to regulate cell polarity and microtubule dynamics in Caenorhabditis elegans, Drosophila, invertebrates, vertebrates, and mammals. An earlier study has shown that MARK4 is present at the ectoplasmic specialization and blood-testis barrier (BTB) in the seminiferous epithelium of adult rat testes. Here, we report the function of MARK4 and another isoform MARK2 in Sertoli cells at the BTB. Knockdown of MARK2, MARK4, or MARK2 and MARK4 by RNAi using the corresponding siRNA duplexes without apparent off-target effects was shown to impair tight junction (TJ)-permeability barrier at the Sertoli cell BTB. It also disrupted microtubule (MT)- and actin-based cytoskeletal organization within Sertoli cells. Although MARK2 and MARK4 were shown to share sequence homology, they likely regulated the Sertoli cell BTB and MT cytoskeleton differently. Disruption of the TJ-permeability barrier following knockdown of MARK4 was considerably more severe than loss of MARK2, though both perturbed the barrier. Similarly, loss of MARK2 affected MT organization in a different manner than the loss of MARK4. Knockdown of MARK2 caused MT bundles to be arranged around the cell periphery, whereas knockdown of MARK4 caused MTs to retract from the cell edge. These differences in effects on the TJ-permeability barrier are likely from the unique roles of MARK2 and MARK4 in regulating the MT cytoskeleton of the Sertoli cell.
Topics: Actin Cytoskeleton; Actins; Animals; Blood-Testis Barrier; Male; Microtubules; Protein Serine-Threonine Kinases; RNA, Small Interfering; Rats; Rats, Sprague-Dawley; Sertoli Cells; Spermatogenesis; Tight Junctions
PubMed: 35971301
DOI: 10.1210/endocr/bqac130 -
Cells Jul 2023Sertoli cells are essential for germ cell development and function. Their disruption by endocrine disrupting chemicals (EDCs) or drugs could jeopardize spermatogenesis,...
Sertoli cells are essential for germ cell development and function. Their disruption by endocrine disrupting chemicals (EDCs) or drugs could jeopardize spermatogenesis, contributing to male infertility. Perinatal exposure to EDCs and acetaminophen (APAP) disrupts male reproductive functions in animals and humans. Infants can be exposed simultaneously to the dietary soy phytoestrogen genistein (GEN) and APAP used for fever or pain relief. Our goal was to determine the effects of 10-100 µM APAP and GEN, alone or mixed, on immature Sertoli cells using mouse TM4 Sertoli cell line and postnatal-day 8 rat Sertoli cells, by measuring cell viability, proliferation, prostaglandins, genes and protein expression, and functional pathways. A value of 50 µM APAP decreased the viability, while 100 µM APAP and GEN decreased the proliferation. Sertoli cell and eicosanoid pathway genes were affected by GEN and mixtures, with downregulation of Sox9, , , and genes relevant for Sertoli cell function, while genes involved in inflammation were increased. RNA-seq analysis identified p53 and TNF signaling pathways as common targets of GEN and GEN mixture in both cell types. These results suggest that APAP and GEN dysregulate immature Sertoli cell function and may aid in elucidating novel EDC and drug targets contributing to the etiology of male infertility.
Topics: Animals; Female; Male; Mice; Pregnancy; Rats; Acetaminophen; Genistein; Infertility, Male; Rodentia; Sertoli Cells
PubMed: 37443838
DOI: 10.3390/cells12131804