Genetic factors in human reproduction a trade off between procreation and longevity

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Genetic factors in human reproduction a trade off between

procreation and longevity

Dunné, F.M. van

Citation

Dunné, F. M. van. (2006, October 18). Genetic factors in human reproduction a trade off between procreation and longevity. Retrieved from https://hdl.handle.net/1887/8781 Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the_{Institutional Repository of the University of Leiden} Downloaded from: https://hdl.handle.net/1887/8781

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GENETIC FACTORS IN HUMAN

REPRODUCTION

A trade off between

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ISBN: 90–8559–212-7

Cover photo: F.M . van Dunné (The hand of my 90 year old grandmother with the hand of my two-month-old son, September 2001)

Printed by: Optima Grafische Communicatie B.V.

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Genetic factors in human reproduction.

A trade off between procreation and l

ongevity

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden, op gezag van de Rector Magnificus Dr.D.D.Breimer,

hoogleraar in de faculteit der W iskunde en Natuurwetenschappen en die der Geneeskunde, volgens besluit van het College voor Promoties te verdedigen op woensdag 18 oktober 2006

klokke 13.45 uur

door

Frédérique Margo van Dunné

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PROMOTIECOMMISSIE

Promotores: Prof. dr. F.M. Helmerhorst Prof. dr. T.W.J. Huizinga Prof. dr. R.G.J. Westendorp

Referent: Dr. Y.T. van der Schouw. (Universiteit Utrecht)

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In memory of my grandfather, Prof. dr. J.J. Dozy 1909-2004

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CONTENTS

Chapter 1 General introduction 9 1. Regulating human lifespan 10 2. Human reproduction 12 2.1 Fecundity 13 2.2 Miscarriage 14 3. Immunology 17 3.1 Cytokines 17 4. Genetics 19 4.1 IL-10 polymorphisms 19 4.2 Factor V Leiden 20 5. Outline of this thesis 21

Chapter 2 Optimizing human fertility and survival 29 Chapter 3 Interleukin-10 promoter polymorphisms in male and female fertility

and fecundity 33

Chapter 4 Miscarriage but not fecundity is associated with progression of joint

destruction in rheumatoid arthritis 47 Chapter 5 Factor V Leiden Mutation in Relation to Fecundity and Miscarriage

in Women with Venous Thrombosis 61 Chapter 6 Gender-specific association of the factor V Leiden mutation with

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Chapter 7 General discussion 87 1. Genetic factors and human reproduction 88 2. Trade off? 88 3. Cytokines and coagulation in pregnancy 90 4. Th-1/Th-2 paradigm in pregnancy? 91 5. A Too easy acceptance of a pregnancy? 93 6. Clinical implications and future research 95 Chapter 8 Summary & Samenvatting 99

Authors and affiliations 107

Publication list 108

Acknowledgements 109

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