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Human Reproduction Update 2013During the seminiferous epithelial cycle, restructuring takes places at the Sertoli-Sertoli and Sertoli-germ cell interface to accommodate spermatogonia/spermatogonial... (Review)
Review
BACKGROUND
During the seminiferous epithelial cycle, restructuring takes places at the Sertoli-Sertoli and Sertoli-germ cell interface to accommodate spermatogonia/spermatogonial stem cell renewal via mitosis, cell cycle progression and meiosis, spermiogenesis and spermiation since developing germ cells, in particular spermatids, move 'up and down' the seminiferous epithelium. Furthermore, preleptotene spermatocytes differentiated from type B spermatogonia residing at the basal compartment must traverse the blood-testis barrier (BTB) to enter the adluminal compartment to prepare for meiosis at Stage VIII of the epithelial cycle, a process also accompanied by the release of sperm at spermiation. These cellular events that take place at the opposite ends of the epithelium are co-ordinated by a functional axis designated the apical ectoplasmic specialization (ES)-BTB-basement membrane. However, the regulatory molecules that co-ordinate cellular events in this axis are not known.
METHODS
Literature was searched at http://www.pubmed.org and http://scholar.google.com to identify published findings regarding intercellular adhesion molecules (ICAMs) and the regulation of this axis.
RESULTS
Members of the ICAM family, namely ICAM-1 and ICAM-2, and the biologically active soluble ICAM-1 (sICAM-1) are the likely regulatory molecules that co-ordinate these events. sICAM-1 and ICAM-1 have antagonistic effects on the Sertoli cell tight junction-permeability barrier, involved in Sertoli cell BTB restructuring, whereas ICAM-2 is restricted to the apical ES, regulating spermatid adhesion during the epithelial cycle. Studies in other epithelia/endothelia on the role of the ICAM family in regulating cell movement are discussed and this information has been evaluated and integrated into studies of these proteins in the testis to create a hypothetical model, depicting how ICAMs regulate junction restructuring events during spermatogenesis.
CONCLUSIONS
ICAMs are crucial regulatory molecules of spermatogenesis. The proposed hypothetical model serves as a framework in designing functional experiments for future studies.
Topics: Blood-Testis Barrier; Cell Adhesion Molecules; Epithelium; Humans; Male; Seminiferous Epithelium; Sertoli Cells; Spermatids; Spermatogenesis; Spermatozoa; Testis; Tight Junctions
PubMed: 23287428
DOI: 10.1093/humupd/dms049 -
Experimental and Clinical... Nov 2021Stroke exacts a heavy toll on death and disability worldwide. In animal studies, cell transplant has shown a positive effect by inducing neurogenesis, angiogenesis, and...
OBJECTIVES
Stroke exacts a heavy toll on death and disability worldwide. In animal studies, cell transplant has shown a positive effect by inducing neurogenesis, angiogenesis, and modulating inflammation. Cell transplant therapy could provide researchers with new strategies for treating stroke. The mechanistic target of rapamycin is a central signaling pathway for coordination and control; the administration of rapamycin, a key modulator of this pathway, could be a new therapeutic approach in neurological disorders.
MATERIALS AND METHODS
Adult rats were grouped into 5 main groups: control, sham, rapamycin receiving, Sertoli cell receiving, and rapamycin plus Sertoli cell receiving groups. Sertoli cells were taken from another rat tissue and injected into the right striatum region. After 5 days, ischemic induction was performed, and rapamycin injection (300 mg/kg) was performed 1 hour before surgery. After 24 hours, some regions of the brain, including the cortex, striatum, and piriform cortex-amygdala, were isolated for evaluation.
RESULTS
Our results showed that infarct volume, brain edema, and blood-brain barrier permeability assessments were significantly reduced in some areas of the brain in rats that received rapamycin plus Sertoli cells compared with results shown in the control group.
CONCLUSIONS
Pretreatment with Sertoli cell transplant plus rapamycin injection may enhance neural survival during ischemia through increased glial cell-derived neurotrophic factor and vascular endothelial growth factor, inhibiting the mechanistic target of rapamycin pathway and increasing autophagy performance.
Topics: Animals; Brain Ischemia; Cell Transplantation; Humans; Infarction, Middle Cerebral Artery; Ischemia; Male; Rats; Sertoli Cells; Sirolimus; Stroke; Treatment Outcome; Vascular Endothelial Growth Factor A
PubMed: 34812711
DOI: 10.6002/ect.2021.0198 -
Frontiers in Endocrinology 2022Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen... (Review)
Review
Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.
Topics: Humans; Male; Receptors, Androgen; Sertoli Cells; Signal Transduction; Spermatogenesis; Testis
PubMed: 35282467
DOI: 10.3389/fendo.2022.838858 -
Cellular and Molecular Life Sciences :... Mar 2013Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible... (Review)
Review
Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.
Topics: Animals; Energy Metabolism; Hormones; Humans; Male; Sertoli Cells; Spermatogenesis
PubMed: 23011766
DOI: 10.1007/s00018-012-1079-1 -
Nature Communications Jan 2020Spermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types. Defects in Sertoli...
Spermatogonia, which produce sperm throughout the male lifetime, are regulated inside a niche composed of Sertoli cells, and other testis cell types. Defects in Sertoli cells often lead to infertility, but replacement of defective cells has been limited by the inability to deplete the existing population. Here, we use an FDA-approved non-toxic drug, benzalkonium chloride (BC), to deplete testis cell types in vivo. Four days after BC administration, Sertoli cells are preferentially depleted, and can be replaced to promote spermatogenesis from surviving (host) spermatogonia. Seven days after BC treatment, multiple cell types can be engrafted from fresh or cryopreserved testicular cells, leading to complete spermatogenesis from donor cells. These methods will be valuable for investigation of niche-supporting cell interactions, have the potential to lead to a therapy for idiopathic male infertility in the clinic, and could open the door to production of sperm from other species in the mouse.
Topics: Animals; Animals, Newborn; Benzalkonium Compounds; Cryopreservation; Dogs; Male; Mice, Inbred Strains; Mice, Transgenic; Organ Culture Techniques; Sertoli Cells; Spermatogenesis; Spermatogonia; Stem Cell Niche; Testis
PubMed: 31896751
DOI: 10.1038/s41467-019-13879-8 -
Cell Reports Apr 2020Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized...
Sertoli cells are supporting cells of the testicular seminiferous tubules, which provide a nurturing environment for spermatogenesis. Adult Sertoli cells are polarized so that they can simultaneously support earlier-stage spermatogenic cells (e.g., spermatogonia) basally and later-stage cells (e.g., spermatids) apically. To test the consequences of disrupting cell polarity in Sertoli cells, we perform a Sertoli-specific conditional deletion of Rac1, which encodes a Rho GTPase required for apicobasal cell polarity. Rac1 conditional knockout adults exhibit spermatogenic arrest at the round spermatid stage, with severe disruption of Sertoli cell polarity, and show increased germline and Sertoli cell apoptosis. Thus, Sertoli Rac1 function is critical for the progression of spermatogenesis but, surprisingly, is dispensable for fetal testicular development, adult maintenance of undifferentiated spermatogonia, and meiotic entry. Our data indicate that Sertoli Rac1 function is required only for certain aspects of spermatogenesis and reveal that there are distinct requirements for cell polarity during cellular differentiation.
Topics: Animals; Cell Differentiation; Cell Polarity; Male; Mice; Mice, Inbred C57BL; Neuropeptides; Seminiferous Tubules; Sertoli Cells; Spermatids; Spermatogenesis; Spermatogonia; Testis; rac1 GTP-Binding Protein
PubMed: 32294451
DOI: 10.1016/j.celrep.2020.03.077 -
Cell and Tissue Research Aug 2020The Sertoli cell (SC) specific connexin43 (Cx43) knockout (SCCx43KO) mouse line is ideal to gain insight into the mechanistic gap junction formation in SC and the...
The Sertoli cell (SC) specific connexin43 (Cx43) knockout (SCCx43KO) mouse line is ideal to gain insight into the mechanistic gap junction formation in SC and the seminiferous epithelium. A method for developing primary SC cultures from these mice was established, validated and successfully characterized via polymerase chain reaction, immunohistochemistry, immunofluorescence (IF), and Western blots (WB). It was evident that both knockout (KO) and wild-type (WT) primary cell cultures were similar in morphology. These highly pure SC cultures were subjected to cell proliferation assays indicating no notable proliferation in cultures of both genotypes. Measurements of cell monolayer integrity indicated significant increases in transepithelial electrical resistance and consequently in tight junction expression of the KO cultures. Using semi-quantitative WB and IF, tight junction protein claudin-11 was analyzed. These results support a role for Cx43 in regulating blood-testis barrier (BTB) function, composition, and dynamics in vitro. Thus, the SC deficient Cx43 cell cultures may provide a valuable in vitro tool for a better understanding of the mechanistic role of Cx43 in spermatogenesis and BTB assembly.
Topics: Animals; Cell Line; Cell Proliferation; Cells, Cultured; Connexin 43; Male; Mice; Mice, Knockout; Primary Cell Culture; Sertoli Cells; Tight Junctions
PubMed: 32328805
DOI: 10.1007/s00441-020-03203-y -
Medicinal Research Reviews Jan 2015Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since... (Review)
Review
Otto Warburg observed that cancerous cells prefer fermentative instead of oxidative metabolism of glucose, although the former is in theory less efficient. Since Warburg's pioneering works, special attention has been given to this difference in cell metabolism. The Warburg effect has been implicated in cell transformation, immortalization, and proliferation during tumorigenesis. Cancer cells display enhanced glycolytic activity, which is correlated with high proliferation, and thus, glycolysis appears to be an excellent candidate to target cancer cells. Nevertheless, little attention has been given to noncancerous cells that exhibit a "Warburg-like" metabolism with slight, but perhaps crucial, alterations that may provide new directions to develop new and effective anticancer therapies. Within the testis, the somatic Sertoli cell (SC) presents several common metabolic features analogous to cancer cells, and a clear "Warburg-like" metabolism. Nevertheless, SCs actively proliferate only during a specific time period, ceasing to divide in most species after puberty, when they become terminally differentiated. The special metabolic features of SC, as well as progression from the immature but proliferative state, to the mature nonproliferative state, where a high glycolytic activity is maintained, make these cells unique and a good model to discuss new perspectives on the Warburg effect. Herein we provide new insight on how the somatic SC may be a source of new and exciting information concerning the Warburg effect and cell proliferation.
Topics: Animals; Cell Proliferation; Glycolysis; Humans; Lactates; Male; Neoplasms; Sertoli Cells
PubMed: 25043918
DOI: 10.1002/med.21325 -
Hormone Research 2006The somatic Sertoli cell plays an essential role in embryonic determination of male somatic sex and in spermatogenesis during adult life. One individual Sertoli cell... (Review)
Review
The somatic Sertoli cell plays an essential role in embryonic determination of male somatic sex and in spermatogenesis during adult life. One individual Sertoli cell supplies a clone of developing germ cells with nutrients and growth factors and it is well established that the number of Sertoli cells present is closely correlated to both testicular size and sperm output. Sertoli cells continue to proliferate and differentiate until the beginning of puberty, when they cease dividing and start nursing the germ cells. At this point in time, the future capacity of the testis for sperm production has thus been determined. Prior to puberty the Sertoli cells are immature and differ considerably with respect to morphology and biochemical activity from the mature cell. The several investigations that have focused on hormonal and paracrine regulation of the functions of the mature cell are reviewed here, but the mechanisms underlying the maturation and general maintenance of well-functioning Sertoli cells remain obscure. An alarming decline in male reproductive health has been observed in several Western countries during recent decades. Disturbance of Sertoli cell differentiation is thought to be involved in the pathogenesis of both a poor sperm count and testicular cancer. It is speculated that environmental agents that disrupt the estrogenic/androgenic balance in the testis may play a role in this connection.
Topics: Animals; Cell Proliferation; Endocrine System; Germ Cells; Hormones; Humans; Male; Models, Biological; Organ Size; Paracrine Communication; Sertoli Cells; Spermatozoa; Testicular Diseases; Testis
PubMed: 16804315
DOI: 10.1159/000094142 -
Endocrinology Sep 2017Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating...
Sertoli cells regulate differentiation and development of the testis and are essential for maintaining adult testis function. To model the effects of dysregulating Sertoli cell number during development or aging, we have used acute diphtheria toxin-mediated cell ablation to reduce Sertoli cell population size. Results show that the size of the Sertoli cell population that forms during development determines the number of germ cells and Leydig cells that will be present in the adult testis. Similarly, the number of germ cells and Leydig cells that can be maintained in the adult depends directly on the size of the adult Sertoli cell population. Finally, we have used linear modeling to generate predictive models of testis cell composition during development and in the adult based on the size of the Sertoli cell population. This study shows that at all ages the size of the Sertoli cell population is predictive of resulting testicular cell composition. A reduction in Sertoli cell number/proliferation at any age will therefore lead to a proportional decrease in germ cell and Leydig cell numbers, with likely consequential effects on fertility and health.
Topics: Aging; Animals; Cell Count; Cell Differentiation; Diphtheria Toxin; Genes, Transgenic, Suicide; Germ Cells; Growth and Development; Leydig Cells; Male; Mice; Mice, Transgenic; Peptide Fragments; Sertoli Cells; Sexual Maturation; Spermatogenesis; Spermatozoa; Testis
PubMed: 28911170
DOI: 10.1210/en.2017-00196