Placenta

A Neglected Experimental Animal

Peter Beaconsfield, Claude Villee, Peter Beaconsfield, Claude Villee

• Publisher: Pergamon
• Year: 2013
• Print ISBN: 9780080244358
• eBook ISBN: 9781483279756
• Topic: Medicine
• Subtopic: Medical Technology & Supplies

Placenta: A Neglected Experimental Animal covers the proceedings of the 1978 round table discussion on placenta held at Bedford College, University of London, under the auspices of the Special Commission on Internal Pollution. The placenta's remarkably complete spectrum of cellular and biochemical activity, as well as its hormonal and endocrinological roles and its short life-cycle, adds to its suitability for studying the processes of cell replication, immune mechanisms, graft acceptance and rejection- and aging. This book is organized into four sections encompassing 19 chapters. Section I emphasizes the process of placental metabolism. This section particularly deals with the principles of metabolic regulation; carbohydrate, fat, and protein metabolism; placenta's endocrine functions; and in vitro and in vivo studies of placental metabolism. Section II highlights the placenta's potential to delineate cell replication processes. This section describes the origin and formation of placenta and the mechanism of carcinogenesis. Section III focuses on the relevance of placenta and its potential as a model for studying malignancy, while Section IV examine its potential as a model for organ aging. This book will be of value to cell and developmental biologists, immunologists, and oncologists.

Section I

Placental metabolic processes

A NEGLECTED EXPERIMENTAL ANIMAL

Editors’ Note: In obstetrics the placenta tends to be taken for granted, except in the rare instances where it appears to fail. As an experimental model it is seldom even considered. Hence the deliberately provocative heading (which also subtitles the proceedings) to this first editorial note. Others introduce each of the later sections and a final one concludes the whole book. Their purpose is simply to guide and inform the reader.

Placental studies are so patently of importance in obstetrics and antenatal care – especially for research into threatened and spontaneous abortion, fetal anomalies, concealed haemorrhage, rhesus incompatibility and other disorders of pregnancy and parturition – that their neglect is hard to explain. Those are not, however, the subject of the placental studies reported here. The meeting on which these proceedings are based was devoted almost exclusively to consideration of the placenta as a research model in five main fields: biochemistry, cell replication, cancer, immunology and ageing. That these types of placental research, more or less remote from obstetric problems, should have been neglected is somewhat easier to understand. Perhaps because there is no obvious connection with childbirth, few have been suggested and fewer still done. But the matter seems to go deeper than that. Animal instincts dictate that the afterbirth should be promptly abandoned or tidied away, often by the mother eating it, while man disposes of the placenta almost ritually by burial or burning. The realistic conclusion that it has no further use seems to be reinforced by a deep but seldom voiced conviction that the placenta should not be exploited for other purposes. Absurd though they seem, such superstitious beliefs may still need to be overcome if the human placenta is to be widely accepted as an experimental model.

Other hinderances also need to be overcome – as indicated in Rebecca Beaconsfield’s opening remarks – if cross-fertilisation by exchange of ideas and information is to take place between different research disciplines and between them and clinical medicine. Such difficulties of communication are not of course peculiar to the placenta. But they also raise primaeval echoes, of tribal identity and territoriality, and they were compounded at this meeting by their technological successor – the complexity of much of the specialised subject-matter. As the edited discussions show, so it may as well be frankly admitted here, few of the assembled experts ventured into each other’s fields …

But then, consider Peter Beaconsfield’s statement that at least a million different biochemical processes are taking place in a typical mammalian cell each second. How many of those do we really know much about? How much less can we hope to understand all the processes of metabolism, growth, immunology and ageing – to name only the fields discussed here – that underlie them? Rash indeed the biochemist who laid claim to such omniscience. Rasher still the specialist in one of these other fields who rushed in with ill-founded comments or suggestions. And yet much progress has come from initially improbable ideas. Indeed, this meeting was planned in part as a forum for generating and refining them – with the first session devoted to the basic biochemical background.

It will be apparent from Eric Newsholme’s opening review that much is now becoming known about the control of biochemical processes. Research is moving on from elucidation of reactions to the mechanisms which determine when, how, why and to what extent they are brought into play. In other words, biochemistry is beginning to be integrated with biological function. Few would question the interdisciplinary value of that development, which is also reflected in the following paper – in which Peter Beaconsfield and Jean Ginsburg discuss placental metabolism, with special reference to carbohydrates, fats and protein.

In the third paper, Hamish Munro turns to higher levels of control – describing what is known about the ways in which nucleic acids direct placental development. Chemical mediators obviously play a major part in transmitting those directions, though little is yet known of their details. But much has recently been learned about a subsequent stage in biochemical control of development, as shown by Dorothy Villee’s review of the endocrine functions of the placenta. The theme of biochemical control is also taken up by Olga Genba

ev discussing prostaglandins in the regulation of placental function.

Towards the end of this first section, Maureen Young describes techniques for studying placental metabolism and transfer, to which David Yudilevich adds a note (in discussion) on a promising new method of investigation.

Finally, drug metabolism: Peter Beaconsfield contributes a personal view of the need for work in this important and neglected field. It is a curious fact that, despite the stimulus the thalidomide disaster gave to drug safety testing in general, relatively little attention has been paid to placental drug metabolism. Yet the placenta does not merely pass most drugs to the fetus. It has the power to modify some and may expose the fetus to higher concentrations of drug or metabolite than are present in the mother. The dearth of work in this field emphasises the need for basic studies – whose practical importance is beyond question.

Much the same can be said of the later sections – on cell replication, immunology and ageing. They make the need for more interdisciplinary meetings unmistakeably clear – and by no means only on the subject of the placenta. The proceedings of this one make no claim to be a definitive review. At best, they make an early staging post on what promises to be a productive way forward.

SECTION I

PLACENTAL METABOLIC PROCESSES

Chairman

Claude Villee

The placenta used to be regarded simply as a barrier between mother and fetus that allowed good things through and kept bad things from reaching the fetus or the mother. But, about 25 years ago, biochemists began to become interested in the placenta, and it was discovered that things went back and forth from mother and fetus, not simply by physical diffusion but by a variety of active transport systems. We now know that the placenta has a full range of metabolic capabilities, and their rate compares favourably with the liver or kidney.

More recently, there has been interest in the synthetic abilities of the placenta, and the studies of its rapid development and ageing provide means of learning about those processes in other tissues. The first papers in this section are concerned with the biochemical background, as most people here are not biochemists. Since we take it for granted that the placenta has all the metabolic capabilities of any other tissue, one of the first questions to be answered is how these various metabolic pathways are regulated.

THE PRINCIPLES OF METABOLIC REGULATION WITH SPECIAL REFERENCE TO DEVELOPMENT AND AGEING

Speaker

Eric A. Newsholme and Bernard Crabtree

Publisher Summary

This chapter discusses the principles of metabolic regulation with special reference to development and ageing. Biochemical research has revealed the various sequences of reactions by which complex substances are degraded to simpler compounds to produce biological energy. It has been shown that a specific series of reactions was responsible for the metabolism of each complex substance and these sequences were called metabolic pathways. The processes needed for the metabolic degradation of complex substances proceed via a series of enzyme-catalyzed reactions because the amount of chemical change that any one enzyme can produce is limited. A large chemical change requires a series of different enzymes. It is likely that a series of related reactions also plays a part in the regulation of cell division and in antibody production. The processes that underlie the phenomena of development and ageing are more complex than the process of glycolysis.

During the earlier part of this century, biochemical research revealed the various sequences of reactions by which complex substances are degraded to simpler compounds in order to produce biological energy. When it became clear that a specific series of reactions was responsible for the metabolism of each complex substance, these sequences were called metabolic pathways (e.g. glycolysis for converting glucose to pyruvate or lactate, and the citric acid cycle for oxidising acetate to carbon dioxide and water. Elucidation of their biochemical details showed each individual reaction in these metabolic pathways to be catalysed by a specific enzyme. In the last 25 years, detailed biochemical research into the molecular details of the individual reactions has been particularly directed to clarifying the catalytic mechanism mediated by each of these enzymes. Another line of investigation, during the same period, has been devoted to the mechanisms which control the rate of the individual reactions in a pathway and hence the flux through the pathway as a whole.

This paper is primarily concerned with regulation, concentrating on general principles rather than the details of individual reactions and pathways. By way of example, reference will be made to glycolysis and glycogenolysis (glycogen...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• CONTRIBUTORS AND INVITED PARTICIPANTS
• FOREWORD
• PLACENTAL PREVIEW
• Section I: Placental metabolic processes
• Section II: Cell replication
• Section III: Immunology
• Section IV: Ageing
• REFERENCES TO PAPERS IN SECTION I
• REFERENCES TO PAPERS IN SECTION II
• REFERENCES TO PAPERS IN SECTION III
• REFERENCES TO SECTION IV
• LOOKING AHEAD
• INDEX