Molecular Biology of the Male Reproductive System (eBook)

David de Kretser (Herausgeber)

eBook Download: PDF | EPUB

2012 | 1. Auflage
483 Seiten
Elsevier Science (Verlag)
978-0-08-091764-1 (ISBN)

Infos

Written by experts in their respective fields, this book reviews the expanding knowledge concerning the mechanisms regulating male reproduction at the molecular and cellular levels. It covers the development of the testes and regulatory controls for spermatogenesis and steroidogenesis, and it considers aspects of Sertoli cell function. Areas of emphasis include communication between the various cell types involved in reproduction by hormone and growth factors and the mechanisms by which these factors regulate gene expression. A number of mammalian systems, including humans, are covered. The carefully selected authors provide a clear synopsis of the concepts in each area as well as the latest references, enabling the reader to investigate the topic further. This book is of interest to those seeking an understanding of the regulatory mechanisms in male reproduction and is written for the graduate and postgraduate levels. - Provides up-to-date reviews of the molecular and cellular biology of male reproduction - Includes chapters on the developmental biology of the testes - Links conventional hormonal control of testicular function with the evolving role of growth factors and proto-oncogenes

Inhalt

Front Cover 1
Molecular Biology of the Male Reproductive System 4
Copyright Page 5
Table of Contents 6
Contributors 16
Preface 18
Chapter 1. Genetic Control of Testis Determination 20
I. Introduction 20
II. SRY, a New Candidate for the Testis Determining Factor 22
III. Biochemical Properties of SRY 29
IV. Perspectives and Conclusions 33
References 35
Chapter 2. Cell Biology of Testicular Development 40
I. Introduction 40
II. Pregonadal Placode 41
III. Gonadal Ridge and Indifferent Gonad 43
IV. Testis 48
V. Basement Membranes and Extracellular Matrix 65
VI. Regulatory Mechanisms 67
References 73
Chapter 3. Nuclear Morphogenesis during Spermiogenesis 86
I. Introduction 86
II. Spermiogenesis 87
III. Principles of Nuclear Shape Determination 90
IV. Elements Possibly Involve din Spermatid Nuclear Shaping 91
V. Specific Forces Required in Spermatid Nuclear Shaping 103
VI. Testing the Roles of Elements in Shaping 107
References 111
Chapter 4. Hormonal Control of Spermatogenesis 118
I. Introduction 118
II. Organization and Kinetics of Spermatogenesis 119
III. Initiation of Spermatogenesis by Testosterone 121
IV. Maintenance and Reinitiation of Spermatogenesis by Testosterone 123
V. Intra testicular Testosterone and Spermatogenesis 127
VI. Initiation of Spermatogenesis by FSH 130
VII. Maintenance and Reinitiation of Spermatogenesis by FSH 131
VIII. Hormonal Control of Male Fertility for Contraception 136
IX. Intratesticular Targets of Testosterone and FSH 137
X. Collaborative Effects of Testosterone and FSH on Spermatogenesis 140
XI. Nongonadotropic Hormones and Spermatogenesis 143
XII. Is the Duration of Spermatogenesis under Hormonal Control? 145
XIII. Summary and Concluding Thoughts 148
References 149
Chapter 5. Patterns of Expression and Potential Functions of Proto-oncogenes during Mammalian Spermatogenesis 162
I. Introduction 162
II. Proto-oncogenes Known to Be Expressed in the Mouse Testis 163
III. Expression of Proto-oncogene-Related Genes in the Testis 185
IV. Summary and Future Directions 186
References 187
Chapter 6. Gene Expression during Spermatogenesis 200
I. Introduction 200
II. Regulation of Gene Expression in Spermatogenic Cells 201
III. Transgenic Mice 219
IV. Genomic Imprinting and Gene Methylation 229
V. Chromosomal Location of Spermatogenic Cell-Specific Genes 234
VI. Conclusions 235
References 237
Chapter 7. Molecular Basis of Signaling in Spermatozoa 252
I. Introduction 252
II. Motility Regulation 253
III. Acrosome Reaction 268
IV. Summary 278
References 278
Chapter 8. Paracrine Mechanisms in Testicular Control 290
I. Introduction 290
II. Germ Cell-Sertoli Cell Cross Talk 290
III. Peritubular–Seminiferous Epithelium Cross Talk 303
IV. Sertoli Cell – Leydig Cell Cross Talk 305
V. Conclusions 312
References 314
Chapter 9. Molecular Biology of Iron Transport in the Testis 330
I. Introduction 330
II. Model of Testicular Iron Transport 331
III. Transferrin 333
IV. Transferrin Receptor 335
V. Ferritin 337
VI. Hemiferrin 338
VII. Stage-Related Expression of Iron Transport Components 340
VIII. Summary 342
References 342
Chapter 10. Molecular Biology of Testicular Steroid Secretion 346
I. Biosynthesis of Testosterone 347
II. Steroidogenic Membranes 362
III. Regulation of Testicular Steroidogenesis 367
IV. Summary and Conclusions 388
References 389
Chapter 11. Hormonal Control Mechanisms of Leydig Cells 402
I. Introduction 402
II. Ontogeny of Tropic Regulation of Leydig Cells 403
III. Molecular Aspects of LH Receptor Function 407
IV. Signal Transduction Systems Involved in LH Action in Leydig Cells 410
V. Effects of Hormones Other than LH on Leydig Cells 416
VI. Conclusions 421
References 422
Chapter 12. Growth Factors in the Control of Testicular Function 430
I. Introduction 430
II. Role of Growth Factors in the Development and Function of Leydig Cells 431
III. Growth Factors and Interactions between the Testis and Immune System 435
IV. Role of Growth Factors in Sertoli Cell Development and Function 440
References 447
Chapter 13. Vascular Controls in Testicular Physiology 458
I. Introduction 458
II. Functional Anatomy of the Testicular Vasculature 459
III. Testicular Blood Flow 463
IV. Testicular Microcirculation 467
V. Local Cellular Control of the Testicular Vasculature 475
VI. Testicular Pathophysiology and Microcirculation 479
VII. Concluding Remarks 480
References 481
Index 488

Textauszug

1

Genetic Control of Testis Determination

V.R. Harley

I Introduction

Jost (1947; Jost et al., 1973) showed that castrated rabbit embryos of either chromosomal sex develop as females, indicating that the presence of testes is necessary for the development of male characteristics. During embryogenesis, the gonad arises as an indifferent tissue, the fate of which follows either the testicular or the ovarian pathway. In mammals, this developmental switch is controlled chromosomally; females have two X chromosomes and males have an X and a Y chromosome. Individuals with a single X chromosome and no Y chromosome (that is, XO) are female (Ford et al., 1959). The presence of a Y chromosome results in male development, regardless of the number of X chromosomes the individual possesses (Jacobs and Strong, 1959; Table 1). Thus, the Y chromosome must encode a dominant inducer of testis formation. The Y-linked gene(s) controlling this process has been named the testis determining factor (TDF; Tdy in mouse). TDF is activated at some time during embryogenesis to commit the undifferentiated genital ridge to the testicular pathway. As a consequence of the action of TDF, subsequent hormonal production induces male sexual differentiation.

Table 1

Chromosomal Basis of Sex Determinationta

Genotype

Phenotype

Female

45, X

Turner’s syndrome

46, XX

Normal

47, XXX

48, XXXX

49, XXXXX

Male

45, X/46, XY

46, XY

Normal

47, XXY

Klinefelter’s syndrome

48, XXYY

49, XXXYY

a The presence of the Y chromosome confers maleness, regardless of the number of X chromosomes.

The gonad is composed of cells derived from four lineages: supporting cells, steroid-producing cells, connective tissue cells, and germ cells. The first signs of male development can be recognized in the genital ridges of mice at 12.5 days post coitum (dpc) when Sertoli cells organize into “testis cords.” Female gonads show no apparent change until 13.5 dpc when the germ cells first enter meiosis (McLaren, 1984). Tdy is thought to act solely in the supporting cell lineage to divert the indifferent gonad away from the ovarian pathway and into the testicular pathway, by triggering supporting cells to differentiate into Sertoli cells rather than into the follicle cells of the ovary (Palmer and Burgoyne, 1991a). Sertoli cells, without further Tdy involvement, then commit the fate of the steroid-producing cells to produce Leydig cells and induce mitotic arrest in the germ cells (Burgoyne et al., 1988). As in other developmental processes, Tdy is presumed to act with other regulatory molecules in the genital ridge to give rise to testes and subsequent male development.

Among humans, rare individuals arise who carry two X chromosomes but are phenotypically male (XX males) or carry a Y chromosome but are phenotypically female (XY females). The molecular analysis of the genomes of these so-called sex-reversed patients led to the isolation of the male sex-determining region Y gene, SRY. Prior to this discovery, candidate Y-located genes had been isolated that subsequently failed to meet established criteria.

This chapter chronicles the identification of a new candidate for the testis determining gene: SRY. Evidence, both circumstantial and direct, that SRY is TDF is outlined. Emphasis is placed on biochemical properties of SRY. Detailed information on the biology of mouse Sry can be found elsewhere (Capel and Lovell-Badge, 1992). The cell and tissue biological processes during sexual differentiation of the gonad are discussed in subsequent chapters.

II SRY, a New Candidate for the Testis Determining Factor

A Mapping the Human Y Chromosome

The approach that proved successful for the isolation of TDF was deletion mapping of the Y chromosome. Almost 60 years ago, Koller and Darlington (1934) observed that X and Y rat chromosomes were dissimilar but could pair along part of their lengths. These researchers proposed that the Y chromosome was composed of a shared region and a Y specific region. The shared or “pseudoautosomal” region (PAR) is terminal on the short arms of the X and Y chromosomes (Pearson and Bobrow, 1970) and would be required for correct pairing during male meiosis. The Y-specific region would encode TDF. Recombination in the PAR region would maintain homology between the X and Y shared regions but recombination should not occur in the Y-specific region (Ferguson-Smith, 1966; Fig. 1). Although cytogenetic analysis of individuals with Y chromosome deletions suggested that TDF was located on the short arm (Goodfellow et al., 1985), precise localization was achieved by studying XX males.

Figure 1 Human X and Y chromosomes. The solid black circle is the centromere, the shaded region is the pseudoautosomal region (PAR), which is the same on both chromosomes, and the solid black line represents the testis determining factor, TDF. Normally, during male meiosis a reciprocal recombination occurs between the X and Y chromosomes that is wholly within the PAR. Occasionally, abnormal crossing over occurs and includes the testis determining factor outside the PAR. This gives rise to two abnormal chromosomes: a Y lacking TDF and an X containing TDF. If these chromosomes are transmitted to the next generation, they give rise to an XY female and an XX male, respectively.

Analysis of the genomes of some XX males showed the presence of Y-derived sequences (Guellen et al., 1984) that presumably arose by aberrant recombination between the X and Y chromosomes (Ferguson-Smith, 1966). Different XX males inherited different terminal fragments, which allowed the construction of a deletion map of the Y chromosome (Affara et al., 1986; Muller et al., 1986; Vergnaud et al., 1986). These maps began to define the minimum region required for male sex determination (Page et al., 1987; Palmer et al., 1989).

B ZFY

Page et al. (1987) further narrowed the region in which TDF must lie as between 140 and 280 kb from the PAR boundary, because an XX male had inherited only 280 kb of Y-derived sequence and part of this region was deleted in an XY female patient with a Y;22 translocation (Fig. 2). On cloning this region and screening by Southern analysis for Y-specific sequences among eutherian mammals, a gene dubbed ZFY was identified. Since ZFY could encode a zinc finger protein and therefore might be a transcription factor, and since mouse Y homologs (Zfy-1 and -2) mapped to a small region known to contain Tdy (McLaren et al., 1988; Roberts et al., 1988; Mardon et al., 1989; Nagamine et al., 1989), ZFY seemed a good candidate for TDF.

Figure 2 Localization of the sex determining region gene SRY on the Y chromosome. The zinc finger gene ZFY, an earlier candidate for TDF, is shown as is the limit of the breakpoints observed in four 46XX males (Palmer et al., 1989). The breakpoints in one XX male and one XY female analyzed by Page et al. (1987) are indicated also. Note that this second deletion, which includes SRY, subsequently was detected in this 46XY female (Page et al., 1990).

However, inconsistencies arose. First it was shown by Sinclair et al. (1988) that the genes homologous to ZFY were not on the marsupial Y chromosome. Further, Koopman et al. (1989) showed that, although Zfy-1 was expressed in the fetal testis of normal mice, expression was absent in homozygous WW mice, which have normal testes but lack germ cells. Finally, Palmer et al. (1989) found four XX males/intersexes who carried less than 60 kb of Y-specific DNA derived from the region adjacent to the PAR boundary but lacked ZFY in their genomes. Collectively, these data firmly rule out ZFY as TDF. The variation in sexual phenotype was suggested to be caused by the proximity of the Y breakpoints to SRY (Palmer et al., 1989).

C Discovery of SRY

Palmer et al. (1989) found that different sized DNA fragments were detected from the four ZFY-negative XX patients when hybridized to a probe 35 kb from the PAR...

Produkt-Details

• Erscheint lt. Verlag: 2.12.2012
• Sprache: englisch
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Histologie / Embryologie
• Themenwelt: Studium ► 1. Studienabschnitt (Vorklinik) ► Physiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-091764-X / 008091764X
• ISBN-13: 978-0-08-091764-1 / 9780080917641