Several methods have been used to demonstrate the vasculature of different organs in man and other species. Many attempts to evaluate the precise microangioarchitecture of organ systems remained unproductive, others were controversial. The development of electron microscope in thirties opend new perspectives in researching microvascular systems. Transmission electron microscopy provided a two-dimensional view on microcirculatory system at higher magnifications, however, its standardization was delayed unnecessarily. The use of methyl methacrylate and related compounds for obtaining replicas of vascular beds, and their study in scanning electron microscope opened a new window in micromorphological research. For the first time, a three-dimensional image analysis of the vascular system was possible. The microvascular corrosion casting method has meanwhile attracted the interest of many contemporary scientists. Its application to medical and biological problems justify it to be used as a routine method for microvascular investigations. The first investigators who used this method, focused either on methodological details or they dealt with the normal microanatomy of organs. The advantages of this method in demonstrating pathological microvascular patterns are also evident.

The ability to "immortalize" immunologically-useful cells by hybridization with a unique cancer cell has revolutionized serological studies and has revealed new potential applications in all fields of biological sciences. This volume presents the studies from a highly successful national symposium on Hybridomas and Cellular Immortality held November 1981 in Houston, Texas. The individual chapters exhibit the diversity of topics discussed during the meeting. These include emphasis on the origin of antibody diversity, Band T lymphocyte differentiation, applications of monoclonal antibodies in studies of histocompatibility, tumor, and viral antigens, plus the use of somatic cell hybridizations for studying T cell products. Three papers focus on the emerging methodologies of in vitro primary immunizations for both humoral and cell-mediated immunities, relevant for coupling with hybridoma technology. There is a useful mix of general (methods) and specific (applications) chapters. A unique aspect of the book is the presentation of both recent research findings with concise descriptions of the state of the art methodologies. It is anticipated that this work will be of interest to a wide audience of practioners in biomedical research. Hopefully, the information contained will foster new and imagi native ideas in hybridoma applications. Baldwin H. Tom, Ph.D. James P. Allison, Ph.D. vii CONTENTS PART L INTRODUCTION TO HYBRIDOMAS 1 Somatic Cell Hybrids and Hybridomas Baldwin H. Tom 3 1. Somatic Cell Hybrids 8 Hybridomas. * * * * * 2.

Leading workers in the field of human reproduction provide both basic knowledge and useful practical information in this book about the most critical phase in the development of a new human being: the first twelve weeks of life. The period from fertilization and implantation to the end of the first trimester is still insufficiently understood and marks a new frontier. The knowledge necessary for applying our present diagnostic capabilities and for venturing into the problematic areas of fertilization technology and embryonic treatment is made easily available in this comprehensive textbook. The book is divided into two parts. The first presents basic information about physiology, anatomy, in vivo investigations, biochemistry and legal aspects. The second part focuses on pregnancy development, monitoring and the clinical diagnosis and management of disorders in the early stages of life. A full section is devoted to assisted conception and the newest possibilities in fertilizationtechnologies, whereby the ethical aspects are also discussed.

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process."

This monograph analyses all aspects related to the etiopathogenesis, pathomorphology, diagnosis and treatment of lumbar disc herniation. It includes 24 chapters, over 500 illustrations, partly in colour, and 2800 bibliographic entries, going from the historical to the most recent ones. Five chapters are dedicated to biological and pathomorphologic aspects both of lumbar disc herniation and the conditions most often associated with herniation. The etiopathogenesis is analysed in the light of the most significant and recent studies. Five chapters deal with the clinical presentation and diagnostic tests in an extremely wide and detailed way. Large space is reserved to conservative management. The chapters on invasive treatments and on the results and complications of surgery define the advantages and limitations of the old and new percutaneous or surgical treatments. Two chapters are dedicated to surgical management of patients with spinal conditions associated with herniation, and two other deal with the surgical failure. This monograph is aimed at satisfying the requirements of both experts and young doctors. Some chapters are of particular interest to the spine specialist, whilst others are useful to the novice to acquire a general knowledge of the subject.

In this book, concerned with the spatial and structural repre- sentation of the cell and its particular specializations, the author hasdeviatedconsiderablyfrom the usual planfor other books related to this subject and has presented the illustrative material in the form of detailed and accurate drawings. The layout of the book provides the reader with a briefnarrative accountoftheparticularorganelleaccompanied byafull-plate illustration on the facing page. Most ofthe narrative accounts areaccompaniedbyashortbibliographyofgermanereferences in the event the reader desires to pursue the subject matter in greater depth. In my estimation there is no other presentation currentlyavailablewhich utilizes thisapproach to demonstrate the cellular components and their associated morphophysi- ology with such elegance. Thetextisclearlywrittenand,althoughtheindividualaccounts are brief, they are highly informative with all ofthe important details being provided. The accuracy ofthe textural presenta- tions and the continuity ofexpression provide strong evidence that the author has spent an enormous amount of time in preparing the text and in painstakingly drawing the illustra- tions. Certainly, an obvious strength ofthis volume is the high qualityoftheillustrativerenditions, allofwhichweredrawnby Dr. KRSTIC. These attest to the profound and comprehensive nature of the author's knowledge of the field of cellular and structural biology. This book is truly a work oflove and art by one who is gifted both didactically and artistically. Dr. KRSTIC should be con- gratulated for providing us with an extremely accurate and detailedaccountofthe 2-dimensional, andinmanycasesthe 3- dimensional, view of the cell and its component organelles. It has no equal.

Preparing manuscripts with figures and tables for camera repro duction was a formidable task. Care has been taken for consistency and typographic accuracy. However, I make no claim that no errors exist in this volume., I hope, however, that the reader will under stand and ignore any error and find this compendious volume useful for numerous biologic studies, physiologic explorations and clinical app lications of radiolabeled cellular blood elements in years to come. M. L. Thakur Editor, and the ASI Director ACKNOWLEDGEMENTS Dr. Max Hardeman of the University of Amsterdam and Dr. Michael Ezekowitz of Yale University served as the codirectors of the Advanced Study Institute (ASI). Dr. Hardeman spent countless hours and contri buted to the scientific program, took care of mailings in Europe, organized transportation in Italy, and communicated with the hotel management on numerous occasions. I cannot thank him enough Dr. Ezekowitz collected some manuscripts and corrected a few. I am grateful to him. I take this opportunity once again to thank all the guest fac ulty, who, despite their busy schedules and time constraints, accepted my invitation and made valuable contributions to the ASI. I am also grateful to all participants, who were so friendly and were primary resources for many lively discussions. They made the ASI profession ally beneficial and socially enjoyable."

Alfons Staudach has been a long-time member of the Anatomic Institute of Karl Franzens University in Graz, where he has devoted particular atten tion to the deeper understanding, appreciation and visualizion of gross ana tomic details. In this work the author has achieved correspondence between sonograms and anatomic sections with a consistency and persuasiveness unequaled in all the previous literature on diagnostic ultrasound. The various planes of section andtheir characteristic features, and indeed the entire format of the text, are designed to provide even the less experienced sonographer with a valuable basis for conducting his examinations. The more experienced reader will find essential information on topographic relations and organ development that is not available in any other work dealing with fetal ana to y. I am certain that my high estimation of this volume will prove justified, and that it will provice its readers with a useful and stimulating resource. Univ. -Prof. Dr. Walter Thiel (Chairman of the Anatomic Institute of the University of Graz) Foreword Anyone setting this book down after an initial perusal must wonder why such a reference was not available ten years ago. The meticulous and fas cinating juxtaposition of gross anatomic sections with sonograms, together with explanatory drawings and many practical guidelines, should enable even the novice accurately to identify details and interpret sonographic findings with precision."

When I was asked by the late Professor Wolfgang Bargmann in 1973 to write the continuation of his review article on the epiphysis cerebri published in the present Handbuch Series in 1943 I felt greatly flattered and readily agreed, not knowing that it is virtually impossible for a single person to cover comprehensively the vast field of pineal research carried out over the last 35 years. Although I have done my best to include as much of the relevant work as possible (up to July 1979), I am constantly haunted by the references I have missed. I sincerely apologize for these omissions: first, to the authors of these papers, who, in addition to working on one of the most stony grounds of biological research, now may experience the additional frustration of not being quoted; secondly, to my fellow pinealogists or pinealogists-to-be, who may carry out painstaking experiments only to find that they have been done before, or who may be led astray because of lack of information. Nevertheless, I do hope that this monograph will fulfil its aim, namely to show how pineal research has progressed over the last 35 years and where it stands today. It is hoped that it will aid in planning relevant experiments and that it shows which approaches to the pineal problem would be better avoided.

Leading international experts contribute to this selection of reviews covering the merging fields of growth factors, differentiation factors, and cytokines. These appear to play fundamental roles in a wide variety of physiological and pathophysiological processes that include the regulation of growth in normal and malignant cells, embryogenesis, the immune response, wound healing, inflammation, and atherogenesis. The major aspects of recent research and development are discussed, providing an important update in this pioneering field.

The advantages of obtaining a completely defined environment for the growth of cells in vitro were recognized very early in the history of cell culture (Lewis and Lewis, 1911). Continued interest in the nutritional requirements of cells in vitro and in providing an optimal environment for cells led to the development of the complex nutrient mixtures available today in many media (Waymouth, 1972; Ham, 1965). However, serum remained an essential component of medium for the growth of most cell types in culture. The question of what factor (or factors) in serum was essential for cell growth and survival remained unanswered for several decades. Initially, experiments were designed to purify the "active component" of serum for the growth of cells in culture. These experiments identified fetuin (Fisher et at., 1958) and nonsuppressible insulinlike activity (Temin et at., 1972) as important components of serum. However, the complexity of serum and the very low levels of active components in serum hindered progress in identi fying and isolating serum factors."

Since 1984, we have organized Satellite Symposia on Retinal Degenerations that are held in conjunction with the biennial International Congress of Eye Research. The timing and location of our Retinal Degeneration Symposia have all owed scientists and clinicians from around the world to convene and present their exciting new findings. The symposia have been arranged to allow ample time for discussions and one-on-one interactions in a relaxed atmos phere, where international friendships and collaborations could be established. The II International Symposium (also known as the Sendai Symposium on Retinal Degeneration) was held in 1986 in Sendai, Japan, on the occasion of the retirement of Kat suyoshi Mizuno as Professor and Chairman of Ophthalmology at Tohoku Medical SchooL On October 5-9, 1996, we returned to Sendai, where the VII International Symposium was held at the Miyagi Zao resort hotel in the beautiful Mt. Zao region of northern Japan. This meeting was held on the occasion of the tenth anniversary of Makoto Tarnai as Pro fessor and Chairman of Ophthalmology at Tohoku Medical School. One afternoon of the meeting contained a special symposium in honor of Professor Tarnai, who has signifi cantly elevated the level and intensity of research on retinal degenerations at his university and in Japan during this past decade.

Since the thalidomide (Contergan) tragedy about 30 years ago the induction of prenatally-induced morphological or functional defects has been an area of extensive research. Risk assessment of prenatally-induced adverse health effects is still a difficult task from both experimental data as well asfrom observations in humans. In the contributions to this book three major aspects are dealt with: - Quantitative extrapolations of experimental data to the situation possibly relevant for man. - The significance for a risk assessment with respect to man of minor or rare structural abnormalities observed in experimental studies - The future need to assess congenital dysfunctions (e.g. of the hormone or the immune system) beside the present evaulation of structural defects. Limitations as well as gaps of the present knowledge in this area of basic and applied research are pointed out. Since the results of prenatally-induced lesions may manifest themselves not only pre- but often not before late postnatally, numerous aspects of structural and functional abnormaldevelopment must be studied in experimental and clinical investigations.

H.P. HIGER 1 In the seventeenth century people dreamed about a machine to get rid of evil spirits and obsessions, which were thought to be the main source of mis fortune and disease. I am not going to question this approach, because in a way it sounds reasonable. They dreamed of a machine that would display im ages from the inner world of men which could be easily identified and named. Somehow these are the roots of MR imaging. Of course, we now view disease from a different point of view but our objectives remain the same, namely to make diseases visible and to try to characterize them in order to cure them. This was the reason for setting up a symposium on tissue characterization. About 300 years later the clinical introduction of MRI has great potential for making this dream come true, and I hope that this symposium has con stituted another step toward its realization. When Damadian published his article in 1971 about differences in T1 relaxation times between healthy and pathological tissues, this was a milestone in tissue characterization. His results initiated intensive research in to MR imaging and tissue parameters. Actually his encouraging discovery was not only the first but also the last for a long time in the field of MR tissue characterization.

The aim of Bladder Research Congress, San Francisco, California, April 23-25, 1998, was to provide a forum for authoritative investigators who are actively involved in the various disciplines which define the leading edges of bladder research. It is important for such investigators to continue to meet regularly for the purpose of discussing the latest developments in their individual fields, to analyze the significance of current research, to discuss new tactics for unresolved problems, to critically evaluate current theories, and to develop new theories and approaches as needed. The two and a half day meeting was organized into five half day sessions, with each session encompassing one of five topics: (1) Epithelial-Mesenchymal Interactions; (2) Ex tracellular Matrix and Muscle; (3) Nerves and Pharmacology; (4) Infection and Immunol ogy; and (5) Oncology. Each session was introduced by a moderator followed by five to six invited expert speakers with time for extensive interaction from the participants. Two late-afternoon poster sessions allowed further interactions between investigators. This book documents the proceedings of the Bladder Research Congress. It is organ ized into the five half-day sessions of the meeting with moderators overview and an edited transcription of discussions that followed each presentation. I would like to thank Sarah Burke and the Office of Continuing Medical Education, USCF; Joanne Hayward, Editorial Assistant; and Miriam Escamilla, Administrative Assis tant. I hope you find this resource useful. Laurence S. Baskin, M.D.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

The present new version of this popular laboratory manual is at the same time the first one of this text in the English language - and this makes me even a little proud, as it reminds me of probably the first collection of monoclonal recipes in English, written by myself, which circulated for a couple of years in many laboratories. In the meantime many researchers have put enormous effort into improving methods for monoclonal antibody production. The proce dures have become more and more standardized and by this have more and more lost the character of magic secrets. Hinrich Peters and Horst Baumgarten, who had followed this good tradition already in the previous edition, written in German, suc ceeded in making laboratory tricks teachable. They had contributed their own experiences in cell culture and immunology, and were able to engage a number of experienced authors to contribute to the work. They were all willing to follow the general concept of this book, which contains a brief theoretical background for the methods described and presents the procedures in a highly organized structure. So the book has retained its shape as a "cook-book," which I especially like."

The brine shrimp Artemia has become an important experimental system for studies of the developmental process. In recent years the shrimp has yielded considerable information on the pattern of development, bio chemistry, and gene structure and expression of crustaceans. This book is a compilation of research activity from twenty five of the most active re search laboratories working with brine shrimp in the above areas. It also represents the proceedings of a NATO Advanced Research Workshop held in Montreal, Canada, August 11-13, 1988. The book contains twenty nine full papers covering the major areas discussed at the workshop. In addition, one page abstracts representing seventeen poster presentations which were given at the workshop, and which were deemed to be most relevant to the theme of the book, are included. These are designated with an al in the Table of Contents following the title of each paper. A considerable amount of discussion which took place during the workshop has not been included in the book because of space limitations. However, the editors will endeavour to make some of this in formation available at a later date through the Artemia Newsletter. In addition to the high percentage of invited speakers who attended and contributed to the workshop, the organizers would like to thank a number of participants who made valuable contributions to the major dis cussion sessions. These include: John Freeman, Michael Horst, Herman Slegers, Jack Vaughn, Frank Conte, Sandy McLennan, Clive Trotman and Patrick Sorgeloos."

To preserve tissue by freezing is an ancient concept going back pre sumably to the practice of ice-age hunters. At first glance, it seems as simple as it is attractive: the dynamics of life are frozen in, nothing is added and nothing withdrawn except thermal energy. Thus, the result should be more life-like than after poisoning, tan ning and drying a living cell as we may rudely call the conventional preparation of specimens for electron microscopy. Countless mishaps, however, have taught electron microscopists that cryotechniques too are neither simple nor necessarily more life-like in their outcome. Not too long ago, experts in cryotechniques strictly denied that a cell could truly be vitrified, i.e. that all the solutes and macro molecules could be fixed within non-crystalline, glass-like solid water without the dramatic shifts and segregation effects caused by crystallization. We now know that vitrification is indeed pos sible. Growing insight into the fundamentals of the physics of water and ice, as well as increasing experience of how to cool cells rapidly enough have enlivened the interest in cryofixation and pro duced a wealth of successful applications."

In textbooks on anatomy, radiology and stead of the normal one. An "accessory ar- surgery only the "normal" arterial blood tery" is a second artery ip addition to the one normally present, without any specifi- supply is usually described. This "nor- mality", however, is sometimes found in cation of size being made. However, there less than 30% of all cases for some arteries, is no general agreement on whether minute but in over 95% for others. Rarely men- vessels with very small diameters and hard- tioned are deviations in the individual ar- ly any significant blood flow should also be tery's origin, topographical localization and considered. the area it supplies. They can be classified The aims of this book were twofold: first, to into two groups: malformations and vari- extract the frequency of arterial anomalies from the literature (often published in inac- ations. Malformations often have a nega- tive influence on the function of the organ cessible journals) and second, to classity under normal circumstances, e.g. if both these arteries by schematic outlines of the basic types.

The examination of excavated human bone finds is mainly the domain of anthropologists and forensic pathologists, the former working with ancient and historical specimens, the latter with modern finds. The methodological and diagnostic approaches to these skeletal finds are the same, regardless of the time of burial. For physical an thropology, bodily human relics are dealt with as historical resources which give clues to ancient population structure, population develop ment, life-style and subsistence. They are thus able to help scientists understand the present state of human populations. The identification of the finds, whether species diagnosis or the evaluation of individual parameters such as sex, age at death, body size and shape, kinship and pathology follows the same procedure used by forensic patholo gists, whose task is the identification of bodily relics in cases of crime, mass disaster and the like. However, there are other disciplines which benefit from excavated bone finds. Anatomy gains insights into the morphological variability of the skeleton in time and place. The implications for modern physi cians and pathologists are at least two-fold: pathological specimens are suitable to unravel the distribution of many diseases and the susceptibility of individuals to pathogens in pre-antibiotic populations. In addition to this epidemiological aspect, exhumed specimens often exhibit advanced states of bone disease which are no longer or only very rarely present in today's industrialized populations because of efficient surgical intervention and pharmacological treatment."

What happens to your body after you have died? Fertilizer? Crash Test Dummy? Human Dumpling? Ballistics Practise? Life after death is not as simple as it looks. Mary Roach's Stiff lifts the lid off what happens to our bodies once we have died. Bold, original and with a delightful eye for detail, Roach tells us everything we wanted to know about this new frontier in medical science. Interweaving present-day explorations with a history of past attempts to study what it means to be human Stiff is a deliciously dark investigations for readers of popular science as well as fans of the macabre. 'Spry, common, sharp-witted survey brings a whole new meaning to the phrase "Life after death"' Sunday Times 'One of the funniest and most unusual books of the year' Entertainment Weekly 'Every chapter packed with more arresting details elegantly humourously expressed than one can hope for' Sunday Telegraph

If you want practical information on how to use this book please refer to "Note to the Readers" p. VII. Histochemistry and cytochemistry are essential tools in biomedical research and routine service laboratories. Most texts on histochemistry fall into one of two categories: 1. Encyclopaedic texts covering all or nearly all information available on the whole or selected parts of histochemistry. 2. Reviews or surveys of methods found to be useful by the author(s). While the former category often appeals to the more philosophically inclined reader, direct guidance on the selection of technique may be difficult to find. In contrast, the latter category are often excellent sources for details on how to perform a particular method with a reasonable chance of success. Consideration of the exact mechanism of staining, of possible reasons for failure, and of alternative techniques are, however, frequently lacking. This book is an introduction to the scientific basis of histochemistry and is intended to provide a background for the selection and development of appro priate methods. It is not a "cook book" and readers expecting exhaustive methodological descriptions will be disappointed. Although most ofthe contributors to this book would not describe themselves as histochemists, they have all at some time found it essential to develop a basic understanding of histochemistry. This book contains the information they would have greatly appreciated ready access to at that time."

Both functions of the mammalian ovary, the endocrine and (synthesis and secretion of steroid hormones) and exocrine (production of ova), depend upon the presence and cyclic growth of follicles, as the depletion of primordial follicles from the ovary leads to cessation of these f-unctions or female reproduction in mammals, or to postmenopausal period in humans. Actually, various fertility and sterility problems at the ovarian level are related to follicles. Therefore, a thorough understanding of the biology of ovarian follicles in mammals is of fundamental interest to a wide variety of academic and scientific disciplines. Study of their structure, function, and control involves mor phology, including ultrastructure, cell biology, physiology, endocrinology, biochemis try, immunology, neurobiology and pharmacology. Zoologists take interest in comparative and evolutionary aspects of biology of ovarian follicles in many different groups of mammals. Agricultural scientists and wildlife biologists need a thorough knowledge of the biology of follicles to control more effectively fecundity in domestic animals and endangered species of mammals. Finally, clinical scientists, toxicologists and physicians want to know the normal and pathological features of ovarian follicles in women, especially in relation to health and the regulation of fertility. Having in view the great importance of studying various aspects of biology of ovarian follicles, numerous papers and reviews on several aspects of ovarian follicles are published annually in a wide variety of scientific journals."

This volume contains the Proceedings of the Serono Symposium on Pre implantation Embryo Development, held in Newton, Massachusetts, in 1991. The idea for the symposium grew out of the 1989 Serono Symposium on Fertilization in Mammals* at which preimplantation development was the predominant suggestion for a follow-up topic. This was indeed a timely subject in view of the recent resurgence of interest in this funda mental phase of embryogenesis and its relevance to basic research and applied fertility studies in humans, food-producing animals, and endangered species. The symposium brought together speakers from a broad range of disciplines in order to focus on key regulatory mechanisms in embryo development, using a wide variety of animal models, and on representative topics in human preimplantation embryogenesis. The culmination of preimplantation development is a blastocyst con taining the first differentiated embryonic tissues and capable of initiating and sustaining pregnancy. The central objective of the symposium was to throw light on the regulation of cellular and molecular events underlying blastocyst formation. It was particularly appropriate that the date of the symposium marked the 20th anniversary of the publication of the classic volume Biology of the Blastocyst, the proceedings of an international workshop held in 1970. This book, which summarized most of the information then available on this topic in mammals, was edited by the pioneer in blastocyst research, Dr. Richard B1andau, who was the guest speaker at the symposium."