Griswold Sertoli Cell Biology

2. Auflage 2014
ISBN: 978-0-12-417048-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 488 Seiten

Sertoli Cell Biology, Second Edition summarizes the progress since the last edition and emphasizes the new information available on Sertoli/germ cell interactions. This information is especially timely since the progress in the past few years has been exceptional and it relates to control of sperm production in vivo and in vitro.
Fully revisedWritten by experts in the fieldSummarizes 10 years of researchContains clear explanations and summaries  Provides a summary of references over the last 10 years

Autoren/Hrsg.

Griswold, Michael D.

Inhaltsverzeichnis

1;Front Cover;1
2;Sertoli Cell Biology;4
3;Copyright Page;5
4;Contents;6
5;List of contributors;12
6;Preface;16
7;1 Sertoli cell anatomy and cytoskeleton;20
7.1;I Introduction;20
7.2;II Sertoli cell morphology;23
7.2.1;A The nucleus;23
7.2.2;B Cytoplasm and membrane interactions;24
7.3;III Sertoli cell cytoskeleton;36
7.3.1;A Actin filaments;36
7.3.1.1;1 Ectoplasmic specializations;36
7.3.1.2;2 Tubulobulbar complexes;39
7.3.2;B Microtubules;43
7.3.3;C Intermediate filaments;44
7.3.3.1;1 Desmosome-like junctions and intermediate filaments;45
7.3.3.2;2 Hemidesmosome-like junctions and intermediate filaments;47
7.3.4;D Regulation of the cytoskeleton;48
7.4;IV Concluding remarks;49
7.5;References;50
8;2 Establishment of fetal Sertoli cells and their role in testis morphogenesis;76
8.1;I Introduction;76
8.1.1;A Highlights/milestones since last volume;76
8.2;II Establishment of the gonadal primordium;77
8.3;III Sertoli cell specification and diversion of molecular development toward the testis pathway;79
8.4;IV Organizational functions of fetal Sertoli cells;82
8.4.1;A Formation of testis cords and establishment of testis-specific vasculature;83
8.4.2;B Coordinate development of the interstitium and its resident cell types;86
8.4.3;C Regression of female reproductive tracts by Amh;87
8.4.4;D Regulation of fetal germ cell development by Sertoli cells;88
8.4.5;E Regulation of testis cord elongation;89
8.5;Summary;90
8.6;References;90
9;3 Early postnatal interactions between Sertoli and germ cells;100
9.1;I Introduction;100
9.2;II Neonatal testis development;101
9.2.1;A Gonocyte development;102
9.2.2;B Sertoli cell development;103
9.3;III Role of Sertoli cells in gonocyte proliferation and migration;104
9.3.1;A Regulation of gonocyte proliferation;104
9.3.2;B Control of gonocyte migration;106
9.4;IV Role of Sertoli cells in formation of primary undifferentiated and differentiating spermatogonial populations;108
9.4.1;A Transition of gonocyte to stem and progenitor spermatogonia;109
9.4.2;B Transition of gonocytes to differentiating spermatogonia;110
9.5;V Concluding remarks;111
9.6;References;111
10;4 The spermatogonial stem cell niche in mammals;118
10.1;I Research advances related to the mammalian SSC niche since 2003;118
10.2;II Principles of stem cell niches in mammalian tissues;118
10.3;III Spermatogonial stem cells;119
10.4;IV Location of the SSC;120
10.5;V Factors governing SSC self-renewal and differentiation;123
10.6;VI The environment inside and outside the niche;127
10.7;VII The role of cell migration in SSC self-renewal and differentiation;128
10.8;VIII Spermatogonial differentiation;129
10.9;IX Niche localization: what controls the controller?;130
10.10;X The SSC niche and the cycle of the seminiferous epithelium;130
10.11;XI The SSC niche during cell loss;131
10.12;XII Perspectives;132
10.13;Acknowledgments;133
10.14;References;133
11;5 DMRT1 and the road to masculinity;142
11.1;I Introduction;142
11.1.1;Doublesex (dsx) and male abnormal-3 (mab-3) related transcription factor and the DM domain;142
11.2;II DMRT1 expression;143
11.3;III Regulation of DMRT1;148
11.3.1;A Endocrine;148
11.3.2;B Temperature;151
11.4;IV DMRT1 locus and gene expression;152
11.4.1;A DMRT1 locus;152
11.4.2;B In silico sequence analysis;154
11.4.3;C DMRT1 5'-flanking region;154
11.4.4;D Distal ECRs;155
11.4.5;E Transcriptional activity;156
11.4.6;F Transient transfection analysis;157
11.4.7;G Transgenic analysis;158
11.4.8;H Posttranscriptional regulation;161
11.5;V DMRT1 function;161
11.5.1;A Sexual identity and gonad differentiation;161
11.5.2;B Sertoli cell functions;162
11.5.3;C Sertoli cell maturation: neonatal and prepubertal gene expression changes;162
11.5.4;D Sertoli cell morphology: integrity, polarity, and nuclear structure;164
11.5.5;E Nuclear structure;164
11.5.6;F Structural integrity and polarity;165
11.5.7;G Antagonizing forkhead box L2 (FOXL2) and Sertoli cell differentiation;167
11.5.8;H Germ cell functions;168
11.5.9;I Gonocyte development;169
11.5.10;J Mitotic–meiotic transition;169
11.5.11;K Pluripotency and cancer;171
11.5.12;L DMRT1 and GCTs in humans;174
11.5.13;M Testis development and infertility in humans;175
11.6;VI Conclusions;177
11.7;References;179
12;6 Hormonal regulation of spermatogenesis through Sertoli cells by androgens and estrogens;194
12.1;I Introduction;194
12.2;II Androgen signaling;195
12.2.1;A Classical testosterone signaling;195
12.2.2;B Nonclassical testosterone signaling;195
12.3;III Testosterone production and action;197
12.4;IV Androgen receptor;198
12.4.1;A AR expression in the testis;198
12.4.2;B Sertoli cell-specific ablation of AR;199
12.5;V The role of androgens in Sertoli cells;201
12.5.1;A Androgens and the blood–testis barrier;201
12.5.2;B Androgens in meiosis;202
12.5.3;C Androgens in spermiogenesis and sperm release;203
12.5.4;D Stage-specific effects of androgens;204
12.6;VI AR-dependent gene expression in Sertoli cells;206
12.7;VII Sertoli cell estrogen signaling (from androgens via aromatase);208
12.8;VIII Conclusions and future perspectives;209
12.9;References;211
13;7 Activins and inhibins in Sertoli cell biology: implications for testis development and function;220
13.1;I Introduction: activin and inhibin link multiple cell types to determine male reproductive health;220
13.2;II General structure and signaling pathways;221
13.3;III Regulation of inhibin and activin production;223
13.4;IV Activin and inhibin function in the adult testis;226
13.5;V Activin and inhibin in the developing testis;231
13.5.1;A Fetal testis expression and function;231
13.5.2;B Postnatal testis: activin at the onset of spermatogenesis;232
13.6;VI The contribution of Smads to regulation of testis development and growth;235
13.7;VII Clinical relevance of activin and inhibin for male reproduction;237
13.8;VIII Concluding remarks: the need to understand signaling crosstalk in the testis;239
13.9;Acknowledgments;240
13.10;References;240
14;8 The initiation of spermatogenesis and the cycle of the seminiferous epithelium;252
14.1;I Introduction and highlights since the last volume;252
14.2;II Differentiation of spermatogonia;252
14.3;III Evidence that RA is required for the initiation of meiosis;254
14.4;IV The initiation of asynchronous spermatogenesis by RA;255
14.5;V Regulation of RA synthesis and degradation in the developing testis;257
14.6;VI Extrinsic versus intrinsic factors;261
14.7;References;261
15;9 Retinoic acid metabolism, signaling, and function in the adult testis;266
15.1;I Introduction;266
15.2;II RA synthesis, signaling, and degradation;266
15.3;III Components of the RA pathway within the adult testis;269
15.3.1;A RA synthesis and degradation;269
15.3.2;B RA signaling;272
15.3.3;C Retinoid binding and storage;273
15.4;IV Maintenance of the spermatogenic cycle by RA;274
15.5;V Sertoli cell contributions to RA function within the adult testis;276
15.5.1;A BTB formation and maintenance;278
15.5.2;B Spermiogenesis;279
15.6;VI The effects of retinoids on Sertoli cell function;280
15.6.1;A The adult Sertoli cell cycle;280
15.6.2;B Sertoli cell proliferation;281
15.6.3;C Sertoli cells as a model for investigating retinoid-regulated oxidative balance;282
15.7;VII Conclusions and remaining questions;283
15.8;References;285
16;10 Stage-specific gene expression by Sertoli cells;292
16.1;I Introduction;292
16.1.1;A Male fertility requirement for the production of millions of sperm per day;292
16.1.2;B Morphological basis for the production of large numbers of sperm required for male fertility;292
16.1.3;C Scope of this review;294
16.2;II Evidence that spermatogenic cells regulate biologically important, stage-specific functions of Sertoli cells;294
16.2.1;A The pioneering work of Parvinen and colleagues;294
16.2.2;B Consequences of genetically altering the expression of two stage-specific genes;295
16.3;III CTSL, a model for the analysis of the function and regulation of stage-specific gene expression;295
16.3.1;A Identification of CTSL as a stage-specific secretory product of Sertoli cells;295
16.3.2;B Identification of domains within the CTSL gene that regulate stage-specific gene expression;297
16.4;IV Stage-specific gene expression as a fundamental characteristic of Sertoli cells;299
16.4.1;A Genome-wide analysis of stage-specific gene expression by Sertoli cells;299
16.4.2;B Stage-specific regulation of the lysosome pathway;304
16.4.3;C Stage-specific expression of genes with related functions;306
16.4.3.1;1 Cytoskeleton (Table 10.4);306
16.4.3.1.1;a The actin cytoskeleton;308
16.4.3.1.2;b The microtubule cytoskeleton;310
16.4.3.1.3;c Intermediate filaments;312
16.4.3.2;2 Signaling molecules;313
16.4.3.2.1;a Kinase anchoring proteins;313
16.4.3.2.2;b Plasma-membrane-associated kinase substrate;313
16.4.3.2.3;c Kinases;317
16.4.3.2.4;d Transcriptional activators and repressors;317
16.4.3.2.5;e Receptors and their ligands;318
16.5;V Future directions;319
16.6;Acknowledgments;319
16.7;References;319
17;11 MicroRNAs and Sertoli cells;326
17.1;I Noncoding RNAs;326
17.2;II miRNAs;327
17.3;III The role of miRNAs in spermatogenesis in vivo;328
17.3.1;A Spermatogenic defects resulting from loss of Dicer in SCs;328
17.3.2;B mRNA and protein dysregulation as a result of loss of DICER in SCs;334
17.3.3;C Spermatogenic defects resulting from loss of DICER or DROSHA in germ cells;336
17.4;IV SC-expressed miRNAs and their functions;338
17.4.1;A Targets and potential functions of SC-expressed miRNAs;338
17.4.2;B Protein classes predicted to be regulated by SC-expressed miRNAs;340
17.4.3;C Functions of germ-cell-expressed miRNAs;341
17.5;V Regulation of SC-expressed miRNAs;342
17.5.1;A Developmental regulation;342
17.5.2;B Hormonal regulation;342
17.5.3;C TGF-ß signaling regulation;345
17.6;VI Perspective;345
17.7;References;346
18;12 Biochemistry of Sertoli cell/germ cell junctions, germ cell transport, and spermiation in the seminiferous epithelium;352
18.1;I Introduction;352
18.2;II Cell junctions and their restructuring during the epithelial cycle in the testis;353
18.2.1;A Background;353
18.2.2;B Types of cell junctions in the testis;353
18.2.3;C Functions of cell junctions in the testis;356
18.3;III Ectoplasmic specialization;359
18.4;IV Spermatid transport and spermiation;360
18.4.1;A Background;360
18.4.2;B Cascade of cellular events at the Sertoli cell/spermatid interface at spermiation;362
18.4.3;C The apical ES/BTB/basement membrane axis;364
18.4.4;D Regulation of spermatid transport and sperm release at spermiation;366
18.4.4.1;1 Cytoskeleton;367
18.4.4.2;2 Focal adhesion kinase;368
18.4.4.3;3 Polarity proteins;369
18.4.4.4;4 Endocytic vesicle-mediated trafficking of proteins;371
18.4.5;E Phagocytosis;373
18.4.5.1;1 Background;373
18.4.5.2;2 Phagocytosis in the testis;373
18.4.5.3;3 Remarks;377
18.5;V Transport of preleptotene spermatocytes at the BTB;377
18.5.1;Background—the BTB;377
18.5.2;A Preleptotene spermatocyte transport at the BTB;378
18.5.3;B A biochemical model of preleptotene spermatocyte transport at the BTB;379
18.5.4;C The role of actin- and tubulin-based cytoskeleton in the transport of preleptotene spermatocytes at the BTB;382
18.5.5;D Involvement of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 in preleptotene spermatocyte transport at the BTB;383
18.6;VI Concluding remarks and future perspectives;384
18.7;Acknowledgments;385
18.8;References;385
19;13 Sertoli cell structure and function in anamniote vertebrates;404
19.1;I Introduction;404
19.2;II Sertoli cell proliferation;405
19.2.1;A Development of existing spermatogenic cysts;405
19.2.2;B Generation of new spermatogenic cysts—Sertoli cell progenitors;410
19.2.3;C Intratesticular sites of Sertoli cell proliferation;413
19.2.4;D Regulation of Sertoli cell proliferation;413
19.3;III Sertoli cell functions;418
19.3.1;A Paracrine relay station;418
19.3.2;B Spermiation;419
19.3.3;C Phagocytosis of apoptotic germ cells and removal of residual sperm;420
19.3.4;D Fate after completion of cyst development;421
19.4;IV Concluding remarks;422
19.5;References;422
20;14 Adult Sertoli cell differentiation status in humans;428
20.1;I Introduction and scope of the chapter;428
20.2;II Development of the adult Sertoli cell population;429
20.2.1;A Proliferation in prepubertal life;429
20.3;III Proliferation and differentiation around puberty;430
20.3.1;A Proliferative ability;434
20.3.2;B Sertoli cell junctions;436
20.3.3;C Protein expression;439
20.3.4;D Morphology;440
20.4;IV Differentiation in adult life;441
20.5;V Human Sertoli cell differentiation and pathology;445
20.6;VI Future perspectives;446
20.7;References;447
21;15 Gene knockouts that affect Sertoli cell function;456
21.1;I Introduction;456
21.2;II Genes identified as essential for normal Sertoli cell development and function through KO studies;461
21.2.1;A Enzymes;461
21.2.1.1;1 Enzymes involved in RA biosynthesis and signaling;461
21.2.1.2;2 Key upstream kinase involved in energy metabolism;462
21.2.1.3;3 Enzyme mediating protein C20-prenylation;463
21.2.1.4;4 A cytoplasmic RNase III involved in small noncoding RNA biosynthesis;463
21.2.2;B Receptors;464
21.2.2.1;1 Cell surface transmembrane receptors;464
21.2.2.2;2 Nuclear receptors;465
21.2.3;C Proteins involved in Sertoli cell-germ cell junctions and in Sertoli cell microtubule networks;465
21.2.3.1;1 BTB structural proteins;466
21.2.3.2;2 BTB regulatory proteins;467
21.2.3.3;3 Proteins involved in ES;468
21.2.3.4;4 Proteins involved in Sertoli cell microtubule network;468
21.2.4;D Transcription factors and transcriptional coregulators;469
21.2.5;E Phagocytosis and endocytosis;471
21.2.6;F Signaling molecules;471
21.2.7;G Protein quality control;472
21.2.8;H Lipid homeostasis;472
21.3;III Lessons learned from the gene KO studies;472
21.3.1;A Cell fate control (i.e., proliferation vs. differentiation) is critical to normal Sertoli cell function;472
21.3.2;B Determinants of normal homeostasis of adult Sertoli cells;474
21.3.3;C Sertoli cells control all three phases of spermatogenesis;475
21.4;IV Approaches to gene ablation in Sertoli cells;476
21.5;V Conclusions and perspectives;478
21.6;Acknowledgments;479
21.7;References;479

Leseproben

1 Sertoli cell anatomy and cytoskeleton
Rex A. Hessa and A. Wayne Voglb,    aReproductive Biology and Toxicology, Department of Comparative Biosciences, University of Illinois, Urbana, IL,    bDepartment of Cellular and Physiological Sciences, Faculty of Medicine, The University of British Columbia, Vancouver, BC Sertoli cell morphology has been thoroughly reviewed in the past from basic light and electron microscopy viewpoints, all of which pointed out the uniqueness of this “mother cell” that sends its cytoplasmic arms as “branches of trees” to hold and nurture the development of germ cells. During the past decade, major advancements in Sertoli cell biology have been made using immunofluorescence and three-dimensional imaging made possible with laser-scanning confocal microscopy. Here, we review our current understanding of Sertoli cell morphology with a specific focus on the cytoskeleton. The relationship of the cytoskeleton to intercellular junctions, ectoplasmic specializations, tubulobulbar complexes, and vesicular transport systems is re-examined. Although newer techniques provide a wealth of data on the molecular components of the Sertoli cell, the results will require additional experimental approaches and careful interpretation to provide consistency in data among anatomy, molecular biology, and cell physiology. Keywords
Testis; Sertoli cell; light microscopy; electron microscopy; immunohistochemistry; cytoskeleton; ectoplasmic specialization; tight junction; blood–testis barrier; tubulobulbar complex I Introduction
Numerous and extensive reviews have been written about basic morphology of the mammalian Sertoli cell [1–9]. The purpose of this chapter is not to repeat all that has been covered in the past, but rather to ask how do we deal with the plethora of new data being generated using morphological techniques previously unavailable in the study of this cell [10]. The first book, titled The Sertoli Cell, was filled with photomicrographs illustrating Sertoli cell morphology [11], which was an appropriate tribute to Enrico Sertoli, the first scientist to publish drawings of the cell, later to be given his family name [12–14]. It took nearly an additional 100 years before electron microscopy revealed the intricate complexities of the Sertoli cell within the seminiferous epithelium [15]. The second book, Sertoli Cell Biology, included a review of the morphological variations in cellular organelles [9]; however, much of the book was devoted to Sertoli cell physiology and molecular biology [16]. So, with regard to Sertoli cell anatomy, what has changed during the past 10 years? Basic Sertoli cell anatomy began with crude drawings published in 1865 [9,13], showing cellular extensions, described as “…branched out that touch two cells…” and holding germ cells in “…the canaliculi, or free, and still shut away in the mother cells.” Thus, the concept of “cellule madri” or “mother cell” was born and subsequent publications have shown the finer details, with descriptions of the Sertoli cell as “…not unlike trees…” with their cytoplasmic arms surrounding germ cells like long branches [17]. These earlier studies attempted to leave the reader with a three-dimensional view of the Sertoli cell (Figure 1.1), sending its thin cytoplasmic processes to envelope germ cells as they moved up and down through the seminiferous epithelium, from basement membrane to the luminal surface. Approximately 40% of the Sertoli cell membrane contacts the surface of the elongated spermatids [19], which results in the extension of thin strands of cytoplasm, sometimes reaching a minimum width of less than 50 nm. The cell’s unique morphology made it difficult to observe intimate relationships between cells with routine histology. Ultrastructural studies later helped to fill the gaps in our understanding of junctional complexes, the blood–testis barrier, spermiation, and Sertoli cell’s phagocytosis of the residual body [10].
Figure 1.1 Sertoli cell illustrations of three-dimensional-like projections of its cytoplasm. Each illustration was adapted from an original figure, and used with permission of the publisher. 1865: Sertoli; [13] 1993: Russell; [5] 1988: Kerr; [18] 1990: Ueno [6]. Long ago, Lonnie Russell recognized the importance of improving morphological techniques for observing Sertoli and germ cell interactions. He was one of the first to use thick, plastic-embedded tissue sections of testis for light microscopy, in addition to using thin sections for electron microscopy [20]. During the past decade, scientists have uncovered a wealth of information on genes and proteins expressed in the testis. These advances in basic knowledge were made possible in part because DNA sequencing of the mouse genome was completed. This sequence of data permitted the identification of potentially important gene products for the production of antibodies, which then could be used to localize the proteins in the testis. Thus, since 2005, two techniques have led the way in the study of reproductive morphology. First, the use of immunohistochemistry became the method of choice for identifying and localizing proteins in the cell. Use of this powerful technique has grown exponentially, as evidenced by a recent publication specifically focused on this technique for the study of spermatogenesis [21]. Second, the development of laser-scanning confocal microscopy provided the ability to three-dimensionally image Sertoli–germ cell interactions with relative ease using immunofluorescence. Our review examines the more general morphological features of Sertoli cells using immunohistochemical and fluorescent markers (Figure 1.2), with a special focus on the cytoskeleton. Immunolocalizations of proteins in the nucleus are fairly simple to interpret if the protein of interest is restricted to the Sertoli cell within the seminiferous epithelium. However, careful interpretation is required for the staining of membrane-associated structures, in which proteins are positioned at the Sertoli–Sertoli junction, the ectoplasmic specialization or the disengagement complex during spermiation. These structural zones of the cytoplasm and membrane show dynamic changes not only during development, but also in a cyclical manner during spermatogenesis [22]. Thus, an accurate interpretation of immunolocalization often requires information from additional methodologies, which can include dual staining of overlapping proteins [23–27], immunoelectron microscopy for precise organelle or membrane identification [23,27–29], in situ hybridization to determine cell-specific mRNA production [30,31], and isolation and culture of Sertoli and germ cells [32–36].
Figure 1.2 Schematic illustration of cytoskeletal distribution in Sertoli cells at different stages during spermatogenesis. Sertoli cells are illustrated in yellow, and spermatogenic cells are in gray. Actin filaments are in red, microtubules are in green, intermediate filaments are in blue, and endoplasmic reticulum is in yellow. This illustrates Sertoli cell’s relationship with germ cell movement within the seminiferous epithelium. Photographic examples are presented to demonstrate how immunohistochemistry and immunofluorescence are helping to expand our understanding of the cell’s anatomy and biochemistry and their contribution to the physiology of spermatogenesis. (A) Actin filaments (green) are seen along the basal junctions but also lining the heads of elongated spermatids; (B) Claudin-11 (red) stains only the basal junctional complex; (C) Actin (green), Rab5 (red) and DAPI (blue for nucleus) show the intricate relationship of these proteins to the tubulobulbar complex; (D) Androgen receptor (brown) stains only the Sertoli cell nucleus in the hamster seminiferous epithelium. II Sertoli cell morphology
A The nucleus
In light microscopy, the Sertoli cell nucleus is a “trademark” structure, easily recognized in the adult testis (Figure 1.3) but less distinguishable from spermatogonia in the perinatal period [9]. This is true across all species studied to date. The nucleus is large in size and takes on numerous shapes but is positioned either parallel or perpendicular to the basement membrane [37]. Often, textbooks describe the nucleus as being triangular in shape [5]. Early observations in rodents suggested large variations in nuclear shape by stage of the seminiferous epithelial cycle [22,37]. However, it is best not to use this feature in any effort to recognize specific stages because all shapes have been observed in all stages in the mouse (Figure 1.3) and the shape does not appear to change significantly in the primate testis [2].
Figure 1.3 Illustration of adult mouse Sertoli cell nuclei (arrows) across all 12 stages. Nuclei perpendicular to the basement membrane are seen in stages I–VI, VIII–XI, while nuclei parallel to the basement membrane are seen in stages VII and XII. Bar=10 µm. The nucleus is also described as residing near the basement membrane [38]—and, most often, that is correct....