- Fully revised
- Written by experts in the field
- Summarizes 10 years of research
- Contains clear explanations and summaries
- Provides a summary of references over the last 10 years
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 revised Written by experts in the field Summarizes 10 years of research Contains clear explanations and summaries Provides a summary of references over the last 10 years
Front Cover 1
Sertoli Cell Biology 4
Copyright Page 5
Contents 6
List of contributors 12
Preface 16
1 Sertoli cell anatomy and cytoskeleton 20
I Introduction 20
II Sertoli cell morphology 23
A The nucleus 23
B Cytoplasm and membrane interactions 24
III Sertoli cell cytoskeleton 36
A Actin filaments 36
1 Ectoplasmic specializations 36
2 Tubulobulbar complexes 39
B Microtubules 43
C Intermediate filaments 44
1 Desmosome-like junctions and intermediate filaments 45
2 Hemidesmosome-like junctions and intermediate filaments 47
D Regulation of the cytoskeleton 48
IV Concluding remarks 49
References 50
2 Establishment of fetal Sertoli cells and their role in testis morphogenesis 76
I Introduction 76
A Highlights/milestones since last volume 76
II Establishment of the gonadal primordium 77
III Sertoli cell specification and diversion of molecular development toward the testis pathway 79
IV Organizational functions of fetal Sertoli cells 82
A Formation of testis cords and establishment of testis-specific vasculature 83
B Coordinate development of the interstitium and its resident cell types 86
C Regression of female reproductive tracts by Amh 87
D Regulation of fetal germ cell development by Sertoli cells 88
E Regulation of testis cord elongation 89
Summary 90
References 90
3 Early postnatal interactions between Sertoli and germ cells 100
I Introduction 100
II Neonatal testis development 101
A Gonocyte development 102
B Sertoli cell development 103
III Role of Sertoli cells in gonocyte proliferation and migration 104
A Regulation of gonocyte proliferation 104
B Control of gonocyte migration 106
IV Role of Sertoli cells in formation of primary undifferentiated and differentiating spermatogonial populations 108
A Transition of gonocyte to stem and progenitor spermatogonia 109
B Transition of gonocytes to differentiating spermatogonia 110
V Concluding remarks 111
References 111
4 The spermatogonial stem cell niche in mammals 118
I Research advances related to the mammalian SSC niche since 2003 118
II Principles of stem cell niches in mammalian tissues 118
III Spermatogonial stem cells 119
IV Location of the SSC 120
V Factors governing SSC self-renewal and differentiation 123
VI The environment inside and outside the niche 127
VII The role of cell migration in SSC self-renewal and differentiation 128
VIII Spermatogonial differentiation 129
IX Niche localization: what controls the controller? 130
X The SSC niche and the cycle of the seminiferous epithelium 130
XI The SSC niche during cell loss 131
XII Perspectives 132
Acknowledgments 133
References 133
5 DMRT1 and the road to masculinity 142
I Introduction 142
Doublesex (dsx) and male abnormal-3 (mab-3) related transcription factor and the DM domain 142
II DMRT1 expression 143
III Regulation of DMRT1 148
A Endocrine 148
B Temperature 151
IV DMRT1 locus and gene expression 152
A DMRT1 locus 152
B In silico sequence analysis 154
C DMRT1 5'-flanking region 154
D Distal ECRs 155
E Transcriptional activity 156
F Transient transfection analysis 157
G Transgenic analysis 158
H Posttranscriptional regulation 161
V DMRT1 function 161
A Sexual identity and gonad differentiation 161
B Sertoli cell functions 162
C Sertoli cell maturation: neonatal and prepubertal gene expression changes 162
D Sertoli cell morphology: integrity, polarity, and nuclear structure 164
E Nuclear structure 164
F Structural integrity and polarity 165
G Antagonizing forkhead box L2 (FOXL2) and Sertoli cell differentiation 167
H Germ cell functions 168
I Gonocyte development 169
J Mitotic–meiotic transition 169
K Pluripotency and cancer 171
L DMRT1 and GCTs in humans 174
M Testis development and infertility in humans 175
VI Conclusions 177
References 179
6 Hormonal regulation of spermatogenesis through Sertoli cells by androgens and estrogens 194
I Introduction 194
II Androgen signaling 195
A Classical testosterone signaling 195
B Nonclassical testosterone signaling 195
III Testosterone production and action 197
IV Androgen receptor 198
A AR expression in the testis 198
B Sertoli cell-specific ablation of AR 199
V The role of androgens in Sertoli cells 201
A Androgens and the blood–testis barrier 201
B Androgens in meiosis 202
C Androgens in spermiogenesis and sperm release 203
D Stage-specific effects of androgens 204
VI AR-dependent gene expression in Sertoli cells 206
VII Sertoli cell estrogen signaling (from androgens via aromatase) 208
VIII Conclusions and future perspectives 209
References 211
7 Activins and inhibins in Sertoli cell biology: implications for testis development and function 220
I Introduction: activin and inhibin link multiple cell types to determine male reproductive health 220
II General structure and signaling pathways 221
III Regulation of inhibin and activin production 223
IV Activin and inhibin function in the adult testis 226
V Activin and inhibin in the developing testis 231
A Fetal testis expression and function 231
B Postnatal testis: activin at the onset of spermatogenesis 232
VI The contribution of Smads to regulation of testis development and growth 235
VII Clinical relevance of activin and inhibin for male reproduction 237
VIII Concluding remarks: the need to understand signaling crosstalk in the testis 239
Acknowledgments 240
References 240
8 The initiation of spermatogenesis and the cycle of the seminiferous epithelium 252
I Introduction and highlights since the last volume 252
II Differentiation of spermatogonia 252
III Evidence that RA is required for the initiation of meiosis 254
IV The initiation of asynchronous spermatogenesis by RA 255
V Regulation of RA synthesis and degradation in the developing testis 257
VI Extrinsic versus intrinsic factors 261
References 261
9 Retinoic acid metabolism, signaling, and function in the adult testis 266
I Introduction 266
II RA synthesis, signaling, and degradation 266
III Components of the RA pathway within the adult testis 269
A RA synthesis and degradation 269
B RA signaling 272
C Retinoid binding and storage 273
IV Maintenance of the spermatogenic cycle by RA 274
V Sertoli cell contributions to RA function within the adult testis 276
A BTB formation and maintenance 278
B Spermiogenesis 279
VI The effects of retinoids on Sertoli cell function 280
A The adult Sertoli cell cycle 280
B Sertoli cell proliferation 281
C Sertoli cells as a model for investigating retinoid-regulated oxidative balance 282
VII Conclusions and remaining questions 283
References 285
10 Stage-specific gene expression by Sertoli cells 292
I Introduction 292
A Male fertility requirement for the production of millions of sperm per day 292
B Morphological basis for the production of large numbers of sperm required for male fertility 292
C Scope of this review 294
II Evidence that spermatogenic cells regulate biologically important, stage-specific functions of Sertoli cells 294
A The pioneering work of Parvinen and colleagues 294
B Consequences of genetically altering the expression of two stage-specific genes 295
III CTSL, a model for the analysis of the function and regulation of stage-specific gene expression 295
A Identification of CTSL as a stage-specific secretory product of Sertoli cells 295
B Identification of domains within the CTSL gene that regulate stage-specific gene expression 297
IV Stage-specific gene expression as a fundamental characteristic of Sertoli cells 299
A Genome-wide analysis of stage-specific gene expression by Sertoli cells 299
B Stage-specific regulation of the lysosome pathway 304
C Stage-specific expression of genes with related functions 306
1 Cytoskeleton (Table 10.4) 306
a The actin cytoskeleton 308
b The microtubule cytoskeleton 310
c Intermediate filaments 312
2 Signaling molecules 313
a Kinase anchoring proteins 313
b Plasma-membrane-associated kinase substrate 313
c Kinases 317
d Transcriptional activators and repressors 317
e Receptors and their ligands 318
V Future directions 319
Acknowledgments 319
References 319
11 MicroRNAs and Sertoli cells 326
I Noncoding RNAs 326
II miRNAs 327
III The role of miRNAs in spermatogenesis in vivo 328
A Spermatogenic defects resulting from loss of Dicer in SCs 328
B mRNA and protein dysregulation as a result of loss of DICER in SCs 334
C Spermatogenic defects resulting from loss of DICER or DROSHA in germ cells 336
IV SC-expressed miRNAs and their functions 338
A Targets and potential functions of SC-expressed miRNAs 338
B Protein classes predicted to be regulated by SC-expressed miRNAs 340
C Functions of germ-cell-expressed miRNAs 341
V Regulation of SC-expressed miRNAs 342
A Developmental regulation 342
B Hormonal regulation 342
C TGF-ß signaling regulation 345
VI Perspective 345
References 346
12 Biochemistry of Sertoli cell/germ cell junctions, germ cell transport, and spermiation in the seminiferous epithelium 352
I Introduction 352
II Cell junctions and their restructuring during the epithelial cycle in the testis 353
A Background 353
B Types of cell junctions in the testis 353
C Functions of cell junctions in the testis 356
III Ectoplasmic specialization 359
IV Spermatid transport and spermiation 360
A Background 360
B Cascade of cellular events at the Sertoli cell/spermatid interface at spermiation 362
C The apical ES/BTB/basement membrane axis 364
D Regulation of spermatid transport and sperm release at spermiation 366
1 Cytoskeleton 367
2 Focal adhesion kinase 368
3 Polarity proteins 369
4 Endocytic vesicle-mediated trafficking of proteins 371
E Phagocytosis 373
1 Background 373
2 Phagocytosis in the testis 373
3 Remarks 377
V Transport of preleptotene spermatocytes at the BTB 377
Background—the BTB 377
A Preleptotene spermatocyte transport at the BTB 378
B A biochemical model of preleptotene spermatocyte transport at the BTB 379
C The role of actin- and tubulin-based cytoskeleton in the transport of preleptotene spermatocytes at the BTB 382
D Involvement of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2 in preleptotene spermatocyte transport at the BTB 383
VI Concluding remarks and future perspectives 384
Acknowledgments 385
References 385
13 Sertoli cell structure and function in anamniote vertebrates 404
I Introduction 404
II Sertoli cell proliferation 405
A Development of existing spermatogenic cysts 405
B Generation of new spermatogenic cysts—Sertoli cell progenitors 410
C Intratesticular sites of Sertoli cell proliferation 413
D Regulation of Sertoli cell proliferation 413
III Sertoli cell functions 418
A Paracrine relay station 418
B Spermiation 419
C Phagocytosis of apoptotic germ cells and removal of residual sperm 420
D Fate after completion of cyst development 421
IV Concluding remarks 422
References 422
14 Adult Sertoli cell differentiation status in humans 428
I Introduction and scope of the chapter 428
II Development of the adult Sertoli cell population 429
A Proliferation in prepubertal life 429
III Proliferation and differentiation around puberty 430
A Proliferative ability 434
B Sertoli cell junctions 436
C Protein expression 439
D Morphology 440
IV Differentiation in adult life 441
V Human Sertoli cell differentiation and pathology 445
VI Future perspectives 446
References 447
15 Gene knockouts that affect Sertoli cell function 456
I Introduction 456
II Genes identified as essential for normal Sertoli cell development and function through KO studies 461
A Enzymes 461
1 Enzymes involved in RA biosynthesis and signaling 461
2 Key upstream kinase involved in energy metabolism 462
3 Enzyme mediating protein C20-prenylation 463
4 A cytoplasmic RNase III involved in small noncoding RNA biosynthesis 463
B Receptors 464
1 Cell surface transmembrane receptors 464
2 Nuclear receptors 465
C Proteins involved in Sertoli cell-germ cell junctions and in Sertoli cell microtubule networks 465
1 BTB structural proteins 466
2 BTB regulatory proteins 467
3 Proteins involved in ES 468
4 Proteins involved in Sertoli cell microtubule network 468
D Transcription factors and transcriptional coregulators 469
E Phagocytosis and endocytosis 471
F Signaling molecules 471
G Protein quality control 472
H Lipid homeostasis 472
III Lessons learned from the gene KO studies 472
A Cell fate control (i.e., proliferation vs. differentiation) is critical to normal Sertoli cell function 472
B Determinants of normal homeostasis of adult Sertoli cells 474
C Sertoli cells control all three phases of spermatogenesis 475
IV Approaches to gene ablation in Sertoli cells 476
V Conclusions and perspectives 478
Acknowledgments 479
References 479
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....
| Erscheint lt. Verlag | 1.12.2014 |
|---|---|
| Sprache | englisch |
| Themenwelt | Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie |
| Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie | |
| Naturwissenschaften ► Biologie ► Zellbiologie | |
| Naturwissenschaften ► Biologie ► Zoologie | |
| Technik | |
| ISBN-10 | 0-12-417048-X / 012417048X |
| ISBN-13 | 978-0-12-417048-3 / 9780124170483 |
| Haben Sie eine Frage zum Produkt? |
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