Immunology of Pregnancy 2013


by

Gérard Chaouat, Olivier Sandra, & Nathalie Lédée

DOI: 10.2174/97816080573371130101
eISBN: 978-1-60805-733-7, 2013
ISBN: 978-1-60805-734-4



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Since a September, 1992, Nature article which read: “Can there be life without LIF?”, researchers now realize that the maternal immune...[view complete introduction]

Table of Contents

Foreword by Armand Bensussan

- Pp. i-ii (2)

Armand Bensussan

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Foreword by Philippe Kourilsky

- Pp. iii-v (3)

Philippe Kourilsky

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Preface

- Pp. vi-x (5)

Gérard Chaouat

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List of Contributors

- Pp. xi-xvii (7)

Gérard Chaouat

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Introduction

- Pp. xviii-xivii (30)

Gérard Chaouat

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Innate and Adaptive Immunity in the Human Female Reproductive Tract: Bridging the Menstrual Cycle with Pregnancy

- Pp. 3-58 (56)

Charles R. Wira, Mickey V. Patel, Mimi Ghosh, Zheng Shen and Marta Rodríguez-García

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Immunity to Sperm: Auto- and Iso Immunization

- Pp. 59-99 (41)

Koji Koyama

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Contraceptive Vaccines: Past, Present and Future

- Pp. 100-134 (35)

Satish K. Gupta

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Immune Markers of Oocyte and Embryo Quality

- Pp. 135-157 (23)

Nathalie Lédée

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MHC Antigens Expression/ Function at the Embryonic Interface. Part A: Major Histocompatibility Complex Class I Unique Expression in Human Trophoblast: Facts, Questions and Controversies

- Pp. 158-174 (17)

Philippe Le Bouteiller

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Part B: Expression of MHC-I Proteins by the Placenta of Domestic and Laboratory Animals

- Pp. 175-200 (26)

Heloisa M. Rutigliano, Aaron J. Thomas and Christopher J. Davies

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Immunology of Implantation, Implantation Failure and Pregnancy. Part A: Regulators of Early Invasion of Trophoblast Cells

- Pp. 201-219 (19)

Pankaj Suman and Satish K. Gupta

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Part B: Dendritic Cells: New Insights in Reproduction

- Pp. 220-237 (18)

Sandra M. Blois, Petra C. Arck and Gabriela Barrientos

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Part C: A Summary of Cytokine Networks and Embryo: A Short Overview

- Pp. 238-279 (42)

Gérard Chaouat

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Part D: Human Implantation

- Pp. 280-312 (33)

Nathalie Lédée and Mona Rahmati

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Part E: Interleukin-10: A Vascular and Anti-Inflammatory Cytokine Connecting the Pieces of the Pregnancy Puzzle

- Pp. 313-334 (22)

Satyan Kalkunte, Tania Nevers, Eliana M.O. Lippe and Surendra Sharma

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Part F: Functional Duality of Mouse Uterine Natural Killer Cell in Pregnancy

- Pp. 335-359 (25)

Patricia D. A. Lima, Valdemar A. Paffaro and Aureo T. Yamada

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Part G: Human Uterine Natural Killer Cell: Friends or Foes of Pregnancy Outcomes

- Pp. 360-376 (17)

Eliana M.O. Lippe, Aureo T. Yamada and Surendra Sharma

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Part H: Factors Elevated during Sexual Intercourse Act to Assist Pregnancy Outcome

- Pp. 377-383 (7)

Mukesh K. Jaiswal, Timothy M. Millers, Alice Gilman-Sachs and Kenneth D. Beaman

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Part I: Substances Secreted by the Preimplantation Human Embryo

- Pp. 384-396 (13)

Georgi Georgiev, Jana Pastuschek, Stefan Neubeck and Udo R. Markert

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Part J: Placental Interferons, Implantation and Pregnancy

- Pp. 397-421 (25)

Fuller W. Bazer

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Part K: Pathophysiology of the Complement System at Feto-Maternal Interface

- Pp. 422-434 (13)

Roberta Bulla, Chiara Agostinis and Francesco Tedesco

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Part L: Toll-Like Receptors and Nod-Like Receptors in Gestational Tissues

- Pp. 435-453 (19)

Vikki M. Abrahams

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Tolerance to the Fetal Allograft. Part A: Is the Fetus an Allograft and is it Object of Immunological Tolerance?

- Pp. 454-524 (71)

Gérard Chaouat

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Part B: Immunoregulation at the Interface by Placental Suppressor Factors

- Pp. 525-535 (11)

Gérard Chaouat

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Part C: Immunological Tolerance / Acceptance of the Semi-Allogeneic Embryo: Decidual Transforming Growth Factors and Tolerance Signaling Molecules

- Pp. 536-555 (20)

David A. Clark and Reginald M. Gorczynski

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Part D: Role of Regulatory T Cells in Human Reproduction

- Pp. 556-577 (22)

Leonardo Fainboim

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Part E: The Role of Cytotoxic Natural Killer (NK) Cells and Regulatory NK Cells in Pregnancy

- Pp. 578-591 (14)

Shigeru Saito, Tomoko Shima, Akitoshi Nakashima and Yi Lin

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Part F: Pathways for Activating Implantation Tolerance in Early Pregnancy

- Pp. 592-613 (22)

Sarah A. Robertson, David J. Sharkey, John E. Schjenken, Alison S. Care and Lachlan M. Moldenhauer

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Immuno Endocrine Interactions: An Example; Progestagen Treatment for Threatened and Recurrent Abortion and Molecular Mechanisms

- Pp. 614-624 (11)

Julia Szekeres-Bartho, Melinda Halasz, Beata Polgar and Agnes Bogdan

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The Maternal Inflammatory Response to Pregnancy

- Pp. 625-648 (24)

Jennifer H. Southcombe and Ian L. Sargent

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Are There Abortions of Immunological Origin? Part A: Animal Models of Spontaneous Immunological Abortions

- Pp. 649-675 (27)

Gérard Chaouat

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Part B: Immunology and Recurrent Pregnancy Loss – Epidemiological Aspects in Humans

- Pp. 676-690 (15)

Ole B. Christiansen

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Part C: Immune Treatments: Recent Developments

- Pp. 691-716 (26)

Edward E. Winger and Jane L. Reed

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Part D: Debates on Immunotherapy for Recurrent Pregnancy Failure

- Pp. 717-723 (7)

David A. Clark

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Part E: Debates on Immunotherapy for Recurrent Pregnancy Failure

- Pp. 724-734 (11)

Gérard Chaouat

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Impact of the Immune System on Trophoblast Invasion and Uteroplacental Blood Flow

- Pp. 735-758 (24)

Raj Raghupathy

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Epidemiology and Immunology of Preeclampsia. Part A: Preeclampsia, Plague of Human Reproduction. The Role of Paternity and Immunological Implications

- Pp. 759-785 (27)

Pierre-Yves Robillard and Gustaaf Dekker

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Part B: Animal Models to Find a Cure for Preeclampsia

- Pp. 786-799 (14)



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Autoimmunity in Association with Pregnancy

- Pp. 800-826 (27)

Norbert Gleicher

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The Control of HIV-1 In Utero Transmission at the Materno-Fetal Interface by Immunological Determinants

- Pp. 827-855 (29)

Héloïse Quillay, Romain Marlin, Marion Duriez, Marie-Thérèse Nugeyre and Elisabeth Menu

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Annex 1: Immunology for Assisted Reproductive Practitioners: A Comprehensive Overview

- Pp. 856-883 (28)

Ae-Ra Han, Alice Gilman-Sachs, Joon W. Kim and Joanne Kwak-Kim

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Annex 2: Glossary and Conclusions

- Pp. 884-902 (19)

Gérard Chaouat, Olivier Sandra and Nathalie Lédée

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Index

- Pp. 903-928 (26)

Gérard Chaouat, Olivier Sandra and Nathalie Lédée

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Foreword

Foreword by Armand Bensussan

For an immunologist, pregnancy remains an enigma although an enormous accumulation of knowledge was achieved during the past decades. Why is the foetus not rejected? In this eBook are described the most recent findings that could possibly answer to this crucial question, as well as the consequences of such discoveries for some important pregnancy associated pathologies, such as preeclampsia and of course recurrent pregnancy loss.

New molecular and cellular networks are now integrated in a rational way in order to propose satisfying models that explain how normal foetus develops and how it avoids an immune attack.

However, we still do not have the whole story that leads the immune tolerance. Interestingly, when I started my research training late 70’s with my mentor Jean Dausset at Saint Louis Hospital in Paris, he was collecting sera from multiparous women for his studies on HLA polymorphism whereas I was trying to isolate T lymphocytes with suppressive activity.

Concerning his work on polymorphism most is now done thanks to the molecular biology approaches. As for the one bearing on suppressor T cells, the concept was there but unfortunately neither the tools nor the knowledge, which allowed Sakaguchi and colleagues to describe for the first time in the mid 90’s the T regulatory cells (Tregs). Nevertheless, are these cells playing a tolerogenic role during pregnancy? More studies are needed to give a final answer to this question since Tregs exhibit distinct mechanisms to exert their function at the steady state and during inflammatory events.

Similarly, what about NK lymphocytes which were initially described as cells exhibiting spontaneous killer activity without previous immunization and were initially proposed to have deleterious action for the foetus? Meanwhile, were described several activating and inhibitory receptors that control NK lymphocyte effector function as well as were identified two distinct functional subsets that have permitted to consider them as potentially benefic for normal pregnancy by secreting cytokines such as VEGF or Angiopoietin 2.

For a “mainstream immunologist”, once we will have discovered the cellular and molecular basis of immune tolerance during pregnancy, which could be the end result of different mechanisms that are used over distinct period of time, then we might be close to manipulate the immune system for avoiding graft rejection and possibly conversely to stimulate immunity for malignancies eradication. Hence, this ebook brings me remembrances of my early years with my mentor in Saint Louis hospital while describing what has evolved since then and paving the way for the future….

Armand Bensussan
Director of Inserm laboratory
Hospital Saint-Louis and University Paris Diderot
France

Foreword by Philippe Kourilsky

“Immunology of Pregnancy 2013” is a major achievement.

Edited by Gérard Chaouat, a life long expert in the field, this eBook involves some 65 contributors, all renown in their respective specialties. The 14 chapters cover the field of reproductive immunology in a very comprehensive fashion.

Immunology of pregnancy occupies a very special place in immunology. It has played a major role in setting some of the initial major concepts of immunology. Then, it has somehow become isolated. This may result from the specific status of human pregnancy as a major issued of high personal and social relevance. Reproduction defects in humans affect large numbers of women and men, and profoundly affect their lives, without being truly considered as “real” diseases. Rather, they were felt to be confined to private life. They had in addition to cope with the many cultural and religious traits that guide individual and social behaviour. This situation has undoubtedly impacted the Science in many indirect ways. For example, there have been many attempts to treat reproductive deficiencies in rather empirical ways that had little to do with basic Science, and were less stringently controlled than standard clinical trials.

To some extent, immunology of pregnancy might be the only field of immunology in which research, for several decades, has been more focused on humans than on animals, especially mouse models. In other areas of immunology mouse, work has largely dominated over human immunology. The recognition of human immunology as a stand-alone area of immunology is a recent phenomenon. It was largely triggered by the emergence of new technologies that allow performing more extensive and profound even basic research on humans directly, without relying on the conclusions derived from mouse models. This shift of balance between research on mice and men is of major importance, because it is now clear that the mouse and human immune systems are significantly different, to the extent that mouse is too often non predictive of what happens in humans. The broad phenotypic diversity of human beings is an other incentive to promote human immunology. It may thus be possible that reproductive immunology was ahead of its time in working extensively on humans –perhaps too much in advance to conquer enough basic scientific knowledge.

On top of this, the main stream of basic immunology has focused for quite some time –and rightly so – on a number of specific immune phenomena and mechanisms such as the generation of diversity (antibodies and TCRs), or more recently the Toll Like Receptors involvement in innate responses. On the contrary, immunology of pregnancy is by essence systemic, with much defined outputs, the prediction of which requires a holistic approach. We all know, however, that the latter requires an extensive understanding of the elements that constitute the system and of their interactions. More Science is obviously needed before a system biology approach of pregnancy can actually be productive. As a matter of fact, the phenomenon of pregnancy is even more complicated and comprehensive than an immune phenomenon such as an immune response. Pregnancy and the reproductive immunology associated with it, involve a broad variety of physiological issues of all kinds. It has to cope with development biology, the endocrine system metabolism, etc. and not only immunology per se. This point can be made for immunology at large. Immunologists too often forget that the immune system is embedded within the entire organism to the extent that it is hardly possible –and actually impossible– to define the borders of the immune system. Immunology of pregnancy thus recapitulates many of the issues that deal with immunology in the broad sense of this word.

This eBook is not only comprehensive. It is also written in a somewhat unusual way, because it calls on history and reports a few anecdotes. This is associated with the unique character of the editor, Gérard Chaouat, as man who has invested his entire scientific life in the discipline. Together with a large number of scientific achievements, he has experienced all sorts of special situations, some of which are indeed worth being reported. On my side, I wish to share one anecdote. Twenty years ago or so, we collaborated and made a nice piece of work in a murine model of abortion. My co-workers had mutated all the aminoacid residues sitting on the surface of the alpha helices of the H-2 Kd molecule. We could thus analyse which MHC residues where involved in the immune reaction leading to abortion. This paper was accepted in a good immunology journal, but at the same time, Gérard was writing a general paper on pregnancy for a book dedicated to the general public. He received the galley proofs at the same time and mixed them up. His general paper was rejected by the immunology journal. Nevertheless the immunology paper was immediately sent to print and published in the book for the general public, because the editors did not notice the substitution. Once published, the paper could not be re-published as such, and this is how a good piece of Science has passed completely unnoticed.

Immunology of pregnancy is a fascinating field. As a few other fields, such as that of vaccination, it is directly rooted into the life of people. This gives a special taste to the science and endows it with a human dimension that imprints the field very significantly –some times, I must say to the expense of scientific rigour in developing human applications, but other times by providing completely new approaches. This eBook is a lively illustration of this combination of high-level advanced science with the more pragmatic questions coming from the people. The eBook includes a huge amount of scientific knowledge and perfectly reflects the past and current state of this particularly complex, essential and fascinating field. It is highly recommendable.

Philippe Kourilsky
Member of the French Académie des Sciences
France


Preface

Reproductive Immunology is (too) often seen as dealing only with the paradox of the survival in a theoretically hostile maternal immune environment of the “foetal allograft “in mammals.

Thus, most authors date its start from 1953 Medawar’s now citation classic.

However, as will be discussed in this eBook, the “danger” theory enunciated by Polly Matzinger states that there is no problem in such an intimate but peculiar, since necessary, tissular relationship. That immunity might threaten Reproduction is for her an evolutionary nonsense. In fact, Matzinger’s interest in Immunology was at least partly triggered by discussions she had about the “paradox” of placental pregnancy long before she even thought she will one day run the famous “ghost lab” at NIH.

We will, of course, indeed discuss her theory in one chapter of this eBook.

But anyway, it is an error to believe the topic is limited to the relationship between the mother and the foetus: the field is dealing with gametes, since they are necessary to Reproduction, and since pregnancy starts with Fecundation. In fact, so did Reproductive Immunology when it started in 1899 as, independently, Landsteiner and Metchnikoff obtained hetero antibodies against sperm. One year afterwards, Metalnikoff obtained the 1st (immobilizing) iso antibodies to spermatozoa by injecting guinea pigs with their own sperm.

This, incidentally, and it is too often forgotten by mainstream Immunologists, was one of the first demonstrations of “horror autotoxicus”, as Erlich would later (re) name autoimmunity.

Much later, the first steps forwards in Reproductive Immunology were these of Voisin, Barber and Delaunay on one hand in 1951, Freund, Lipton, and Thompson in 1953.

These were followed by Medawar’s lecture, and the seminal experiments of Billingham, with Beer, and later on Head.

It is interesting and noteworthy to recall that when I joined, initially for what would become my Md. Thesis and my first real Scientific paper the INSERM U23 lab, under Guy Voisin’s direction, I was placed in the same room as Marta d’Almeida, Françoise Chadenier and Francine Toullet, who while working on anti sperm immunity taught me the initial steps in Immunology.

In Francine’s lab, the top techniques at the time were sperm cytotoxicity and sperm agglutination for assessment of humoral immunity, as well as DTH measurements by Evans blue rat skin permeation and DTH caliper measurements of footpad swelling.

Another part of the unit was testing whether or not T and B cells were morphologically distinguishable including by electron microscopy studies conducted by Philippe le Bouteiller and Simone Righenzi…

The discovery of T and B cells cooperation, Gershon’s description of Ts (now rejuvenated as T regs) hit the field, as well as NK cells, albeit I must admit that when Herbermann described initially Natural killing, a 5% max killing of Yac-1 target cells in a 51 Cr CRT was judged by many as an artefact. Of course, at that time the mains controversies were centring on the eventual existence of paternal MHC antigens at the interface, whereas it was also the age of the first lectures in Saint Antoine and Pasteur of GP Talwar about the future of contraceptive vaccines (anti hCG).

40 years afterwards, we are no longer dealing with “lymphocytes” and antibodies, but with a variety of cell populations, which we can isolate, thanks not to their morphology, but to a variety of cell surface or cytoplasm markers. Cell to cell communication is effected by a variety of well defined soluble molecules (while many of the “factors” which were described in the dawn of cellular immunology such as Ag-specific TsF, including “TsF1” and “TsF2”, genetically restricted macrophage helper factor, etc… have joined the infamous I-J region in oblivion).

When Tom Wegmann wrote –and it was a conceptual revolution- that the embryo is bathed in a sea of cytokines, he was referring to at best 10 of them, and Tim Mossman had just delineated Th1 from Th2 cells/cytokines.

Now we have more than 35 interleukins, several super families, toll receptors. We know that contraceptive vaccines are feasible (including, one forgets it often, in animal species, where one, for example, has helped to control fox mediated rabies propagation). In fact, Immunology is too often neglected by many obstetricians, who seem to forget (ignore?) Nature’s Editorial “would there be life without LIF”, pinpointing by then that immune molecules can be necessary for pregnancy.

Another reassessment was the realization of the role of NK cells, “killers become builders”….

And so on….

Thus, the field is now established by its own. Parallel developments in ART have emphasized, I repeat, that Immunology could be as important as Endocrinology, whereas more and more facts are implying Immunology in such syndromes as pre eclampsia.

But it is a rapidly moving field, so, albeit the last (and excellent it is) treatise dates from only 2006, the need for another update emerged. The eBook format is excellent in that respect, allowing relatively rapid publication and possibly regular rapid updates.

Hence, this publication appears.

In keeping with the rapid evolution of the discipline, I preferred not to be preposterous, and thus to name it “Immunology of Pregnancy 2013” rather than another “Immunology of Pregnancy”.

Now, who should read this eBook?

Mainstream Immunologists, whose presence on this planet has been dependent on Immunological intervention, a fact they are for most of them surprisingly unaware: but they should also discover a very fascinating New World, and I recall the surprise of a major actor in the cytokine field, who actually discovered the first Interleukin (IL-1), after a lecture I gave at the FIMSA (Federation of meeting, in Hang Zhou, China “I never thought there were so many important cytokines in the uterus!”.

But this eBook is also aimed at Gyn/Obs clinicians…. I know that Immunology has its Jargon, but this is as inescapable as “strangeness” in Nuclear physics and cosmology. Without suggesting the clinicians to make a similar effort as the one required for a Beotian to enter quantum mechanics, we really believe that comprehension of Immune events of pregnancy is now a must for them, and will lead them to new diagnosis and therapeutic tools/ behaviour.

Finally, this eBook is of course aimed at the old and, more important the young Scientists in the field.

To them, we state that “we hope that this eBook is made for you”…

We have tried to encompass most of the important topics (with the exception of Allergy and the foetus and neonate, a topic which deserves a specialized treaty, per se, and stress, since Neuro Immunology is a field by itself, albeit we allude to it in several sections).

Finally, of course I thank here the numerous co-authors for their dedication to the task of writing a relatively concise but complete sub chapter or chapter

Megève, French Alps, August 1st 2011. Paris 1st May 2012.

Gérard Chaouat
Director of Research Emeritus
U976 INSERM/UMR 976 CNRS Hôpital Saint Louis 75010
Paris
France

P.S. Three Last Words:

  1. The views expressed in the chapters are my own, and do not commit any of the other contributors.
  2. The chapters in this eBook are made so that, albeit they complete each other, each one can be read independently. Thus, “redites” are unavoidable, and in fact necessary, as are left contradictive opinions when a matter remains controversial.
  3. The eBook planned originally a chapter on Immunity and Infection /parasites during pregnancy. Because of health problems and then death of the principal author for this chapter, this plan had to be abandoned (see last pages). But we hope, thanks to the eBook format, to be able to provide later on this chapter in electronic form.


List of Contributors

Editor(s):
Gérard Chaouat
Hopital Saint Louis Paris
INRA Jouy en Josas
France


Olivier Sandra
Hopital Saint Louis Paris
INRA Jouy en Josas
France


& Nathalie Lédée
Hopital Saint Louis Paris
INRA Jouy en Josas
France




Contributor(s):
Aaron J. Thomas
Department of Animal, Dairy and Veterinary Sciences
Center for Integrated BioSystems
Utah State University
Logan
UT, 84322-4700
USA


Ae-Re Han
Reproductive Medicine, Department of Obstetrics
Gynecology the Chicago Medical School at Rosalind Franklin University of Medicine and Science
North Chicago
IL, 60064
USA


Agnes Bogdan
Department of Medical Microbiology and Immunology
Medical School, Pécs University
Pécs
Hungary


Akitoshi Nakashima
Department of Obstetrics and Gynecology
University of Toyama
Toyama, 930-0194
Japan


Alice Gilman-Sachs
Department of Microbiology and Immunology
Rosalind Franklin University of Medicine and Science
North Chicago
IL, 60064
USA


Alison S Care
Robinson Institute, School of Pediatric and Reproductive Health
University of Adelaide
Adelaide
SA, 5005
Australia


Aureo T. Yamada
Department of Histology and Embryology
Institute of Biology, University of Campinas
Campinas
SP
Brazil


Beata Polgar
Department of Medical Microbiology and Immunology
Medical School, Pécs University, Pécs, Hungary
Héloïse Quillay Regulation of Retroviral Infection Unit
Department of Virology, Institut Pasteur
Paris
France


Charles R. Wira
Department of Physiology and Neurobiology Dartmouth Medical School
One Medical Center Drive Lebanon
NH, 03756
USA


Chiara Agostini
Institute for Maternal and Child Health, IRCCS Burlo Garofolo
Trieste
Italy


Christopher J. Davies
Department of Animal, Dairy and Veterinary Sciences
Center for Integrated BioSystems
Utah State University
Logan
UT, 84322-4700
USA


David A. Clark
Depts. Medicine, Molecular Medicine & Pathology
Obstetrics & Gynecology, Department of Medicine Room 3H1E
Health Sciences Center, McMaster University
1280 Main St West
Hamilton
Ontario, L8S 4K1
Canada
/
and Toronto General Research Institute
101 College St. Mars Tower TMPT East 2-804
Toronto
Ontario, M5G 1L7
Canada
/
And Professor of Immunology, Faculty of Medicine
University of Toronto
Toronto
Ontario
Canada


David J. Sharkey
Robinson Institute, School of Pediatric and Reproductive Health
University of Adelaide
Adelaide
SA, 5005
Australia


Edward E. Winger
Laboratory for Reproductive Medicine and Immunology
San Francisco
CA, 94111
USA


Eliana M. O. Lippe
Department of Pediatrics
Women and Infants Hospital-Warren Alpert Medical School of Brown University
Providence
Rhode Island
USA


Elisabeth Menu
Regulation of Retroviral Infection Unit, Department of Virology
Institut Pasteur. 25 rue du Dr Roux
Paris, 75015
France


Francesco Tedesco
Department of Life Sciences
University of Trieste, via Valerio 28
Trieste, 34127
Italy


Fuller W. Bazer
442D Kleberg Centre Texas A&M University College Station
TX, 77843-2471
USA


Gabriela Barrientos
Medicine University of Berlin
CC12 Internal Medicine and Dermatology
Laboratory of Reproductive Medicine
Berlin
Germany


Georgi Georgiev
Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia
Bulgaria and Placenta-Labor, Department of Obstetrics
University Hospital Jena
Germany


Gérard Chaouat
Director of Research Emeritus
U976 INSERM /UMR 976 CNRS Hôpital Saint Louis
Paris, 75010
France


Guillermina Girardi
The University of Edinburgh MRC Centre for Reproductive Health
The Queen's Medical Research Institute
47 Little France Crescent EH16 4TJ
Edinburgh
United Kingdom


Gustaaf Dekker
Head Women’s and Children’s Division
Lyell McEwin Hospital, University of Adelaide
Haydown Road
Elizabeth
Vale, 5112
South Australia


Heloisa M. Rutigliano
Department of Animal, Dairy and Veterinary Sciences
Center for Integrated BioSystems
Utah State University
Logan
UT, 84322-4700
USA


Ian L. Sargent
Nuffield Department of Obstetrics and Gynecology
University of Oxford
John Radcliffe Hospital
Oxford , OX3 9DU
United Kingdom


Jana Pastuschek
Placenta-Labor, Department of Obstetrics
University Hospital Jena
Germany


Jane L. Reed
Laboratory for Reproductive Medicine and Immunology
San Francisco
CA, 94111
USA


Jennifer H. Southcombe
Nuffield Department of Obstetrics and Gynecology
University of Oxford
John Radcliffe Hospital
Oxford, OX3 9DU
United Kingdom


Joanne Kwak-Kim
Reproductive Medicine, Department of Obstetrics and Gynecology
The Chicago Medical School at Rosalind Franklin University of Medicine and Science
830 West End Court, Suit 400
Vernon Hills
IL, 60061
USA


John E. Schjenken
Robinson Institute, School of Pediatric and Reproductive Health
University of Adelaide
Adelaide
SA, 5005
Australia


Joon W. Kim
Department of Medicine, Division of Rheumatology
North Western University, Feinberg School of Medicine
Chicago
IL, 60611
USA


Julia Szekeres-Bartho
Department of Medical Microbiology and Immunology
Medical School, Pécs University
Pécs
Hungary


Kenneth D. Beaman
Department of Microbiology and Immunology
Rosalind Franklin University of Medicine and Science
North Chicago
IL, 60064
USA


Koji Koyama
Obstetrics and Gynecology, Laboratory of Developmental Biology and Reproduction
Advanced Medical Sciences, Hyogo College of Medicine
Nishinomiya
Japan


Lachlan M. Moldenhauer
Robinson Institute, School of Pediatric and Reproductive Health
University of Adelaide
Adelaide
SA, 5005
Australia


Leonardo Fainboim
Immunogenetics Laboratory, Clinical Hospital, Department of Microbiology and Immunology
School of Medicine, Buenos Aires University, Argentine National Council for Scientific
Technological Research
Argentina


Marie-Thérèse Nugeyre
Regulation of Retroviral Infection Unit
Department of Virology, Institut Pasteur
Paris
France


Marion Duriez
Regulation of Retroviral Infection Unit
Department of Virology, Institut Pasteur
Paris
France


Marta Rodríguez-García
Department of Physiology and Neurobiology Dartmouth Medical School
One Medical Center Drive Lebanon
NH, 03756
USA


Melinda Halasz
Department of Medical Microbiology and Immunology
Medical School, Pécs University
Pécs
Hungary


Mickey V. Patel
Department of Physiology and Neurobiology Dartmouth Medical School
One Medical Center Drive Lebanon
NH, 03756
USA


Mimi Ghosh
Department of Epidemiology and Biostatistics
George Washington University
2100W Pennsylvania Ave
Washington
DC, 20037
USA


Mona Rahmati
U 976 INSERM U976 INSERM /UMR 976
CNRS Saint Louis Hospital
Paris, 75010
France


Mukesh K. Jaiswal
Department of Microbiology and Immunology
Rosalind Franklin University of Medicine and Science
North Chicago
IL, 60064
USA


Nathalie Lédée
U 976 INSERM U976 INSERM /UMR 976
CNRS Saint Louis Hospital
Paris, 75010
France


Norbert Gleicher
Medical Director and Chief Scientist
Center for Human Reproduction
New York
N.Y
USA
/
President. Foundation for Reproductive Medicine
21 East 69th Street
New York
NY, 10021
USA


Ole B. Christiansen
Fertility Clinic 4071, Rigshospitalet, Co penhagen
Department of Obstetrics and Gynecology
Aalborg hospital
Aalborg
Denmark


Olivier Sandra
INRA, UMR1198 Biologie du Développement et Reproduction
F-78352 Jouy-en-Josas, France; ENVA
Maisons Alfort, F-94704
France


Pankaj Suman
Reproductive Cell Biology Laboratory
National Institute of Immunology Aruna Asaf Ali Marg
New Delhi
India


Patricia D. Lima
Department of Histology and Embryology
University of Campinas, Campinas, SP, 2- Department of Cell
Tissue and Developmental Biology, Institute of Biomedical Science
Federal University of Alfenas
MG
Brazil


Petra C. Arck
Laboratory for Experimental Feto-Maternal Medicine
Department of Obstetrics and Foetal Medicine
University Medical Centre Hamburg-Eppendorf
Hamburg
Germany


Philippe Le Bouteiller
INSERM UMR1043, CNRS UMR5282, Université de Toulouse
Centre de Physiopathologie de Toulouse-Purpan
Hôpital Purpan
Toulouse Cedex 3
BP , 3028 31024
France


Pierre-Yves Robillard
Neonatology
Centre Hospitalier Régional Sud-Réunion
BP 350. Saint-Pierre Cedex
Réunion,
France


Raj Raghupathy
Path Department of Microbiology
Faculty of Medicine Kuwait University
Kuwait


Reginald M. Gorczynski
University of Toronto
Toronto
Ontario
Canada


Roberta Bulla
Department of Life Sciences
University of Trieste
Trieste, 34127
Italy


Romain Marlin
Université Bordeaux 2
UMR-CNRS-5164-CIRID
Bordeaux
France


Sandra M. Blois
Medicine University of Berlin, CC12 Internal Medicine and Dermatology
Laboratory of Reproductive Medicine
Berlin
Germany


Sarah A. Robertson
Robinson Institute, School of Pediatric and Reproductive Health
University of Adelaide
Adelaide
SA, 5005
Australia


Satish K. Gupta
National Institute of Immunology Chief, Reproductive Cell Biology Laboratory
National Institute of Immunology Aruna Asaf Ali Marg
New Delhi
India


Satyan Kalkunte
Department of Pediatrics
Women and Infants Hospital-Warren Alpert Medical School of Brown University
Providence
Rhode Island
USA


Shigeru Saito
Department of Obstetrics and Gynaecology
University of Toyama
Toyama, 930-0194
Japan


Stefan Neubeck
Placenta-Labor, Department of Obstetrics
University Hospital Jena
Germany


Surendra Sharma
Department of Pediatrics
Women and Infants Hospital-Warren Alpert Medical School of Brown University
Providence
Rhode Island, 02912
USA


Tania Nevers
Department of Pediatrics
Women and Infants Hospital-Warren Alpert Medical School of Brown University
Providence
Rhode Island
USA


Timothy M. Miller
Department of Microbiology and Immunology
Rosalind Franklin University of Medicine and Science
North Chicago
IL
USA


Tomoko Shima
Department of Obstetrics and Gynecology
University of Toyama
Toyama, 930-0194
Japan


Udo R. Markert
Placenta-Labor, Department of Obstetrics
University Hospital Jena
Germany


Valdemar A. Paffaro Jr
Department of Cell, Tissue and Developmental Biology
Institute of Biomedical Science
Federal University of Alfenas
MG
Brazil


Vikki M. Abrahams
Department of Obstetrics, Gynaecology & Reproductive Sciences
Yale University School of Medicine
310 Cedar Street, LSOG 305C
New Haven
CT, 06510
USA


Yi Lin
Department of Obstetrics and Gynaecology
Institute of Obstetrics and Gynaecology
Renji Hospital
Shanghai, 200001
China


Zheng Shen
Department of Physiology and Neurobiology Dartmouth Medical School
One Medical Center Drive Lebanon
NH, 03756
USA




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