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Acknowledgments

I would rst like to thank the members of the jury for taking the time to read the present manuscript, which turned out a bit longer than I had planned. I would like to thank Uriel Hazan for accepting to be the president of this jury, book-ending his involvement in my studies. What had started at the ENS Cachan and continued during my Master's degree at the Institut Pasteur, would like to sincerely thank Jean-Luc Battini and Olivier Schwartz for their critical reading and evaluation of the present manuscript and their positive feedback. Finally, I want to thank Pascale Chavatte-Palmer and François Mallet, for taking the time to read my work and for accepting to be a part of the jury. I would, of course, also like to thank Thierry Heidmann for giving me the opportunity to work in his laboratory for the past four years, for being always available when I was in need of a guiding hand and present when I needed some prodding. Thank you for not only helping me to get these results, but also for the countless hours we spent to turn them into actual scientic articles. I am grateful to Anne Dupressoir and Gérard Pierron for spending time reading through my manuscript and their words of encouragement and advice. I also want to thank Christa Kuhn for her enthusiasm and encouragement, which played an important part in getting me to where I am today.

Je souhaite remercier l'intégralité de l'unité 9196, en particulier Marie et Anne pour avoir

partagé leurs savoirs, leurs conseils ainsi que leurs bureaux, Cécile Vernochet pour son aide inestimable, Seila pour son soutien administratif et émotionnel, Grégoire pour son optimisme

inébranlable et infectieux, Caroline, Cécile Lemaître et Anthony pour les bon moments passés

ensemble, et ce-dernier tout particulièrement pour nos nombreuses discussions (profondes et/ou

inutiles) et son énergie aussi inépuisable qu'insupportable. Un grand merci également à Guil-

laume, ex-membre de l'unité, pour m'avoir encadré pendant mes débuts et avoir toujours été

disponible pour mes questions. J'aimerais remercier le gang des pasteuriens, premiers parmi eux mes ex-colocataires, Matthieu et Thomas, merci de m'avoir supporté pendant ces trois ans et quelques de vie com- mune au 20 avenue d'Ivry, qui s'est transformé en haut-lieu de la science, accueillant maints et maints congrès réunissant la ne eur de la virologie et de l'immunologie parisienne. I would iii like to thank Oksana, one of the kindest and most generous persons I have had the pleasure to

know and someone you can always count on. Merci à Simon l'invisible, ton rétro nous a apporté

de nombreuses heures de bonheur. Merci à Vincent le sale cylon pour les côtes de b÷uf et à

ambiance, et je vous souhaite bien du courage, à Juju pour supporter Matthieu et à Juju pour

nir ta thèse. Merci aussi à Anaïs, Laura, Cécile, Alix, Marion et tous les autres qui ont rendu

la vie parisienne tellement plus agréable. J'aimerais également remercier mes nouveaux ex-colocataires, Raphaël, Ferretti et Viking, pour m'avoir permis de garder l'appartement quelques mois de plus, puis pour m'avoir accueilli sur notre canapé qui, entretemps, était devenu le leur. On a somewhat stranger note I would like to thank all of the friends I have never met, but who have been there to play, talk and just hang out in the virtual parts of this world. Thank you to all sigmas, especially 48, Mori Kaal and koreamax, but also willemd, :goatdrügs:, Cal, and even Thuneral, Slap Chop and Koahi. A great thank you to the Aqueduct Acrobats who have been able to observe my slow and Topaz with his awful K/D, expensive haircuts and shared disgust of terrible book adaptations, mrcompson for our academia themed diversions and unmasking the terrible truth behind omics- conferences, and Malloot, everyone's favorite tactical espionage action ground team leader and platforming liability. I also want to thank Norns and Tarth, our resident Americans, as well as

Charisma and Waka.

meinen beiden Brüdern, von deren Hilfe ich immer ausgehen konnte und deren Gesellschaft und Vertrauen mein Leben bereichert haben. Ich danke meiner Oma und meinem Opa für ihre Ermutigungen und Liebe. J'aimerais remercier Patrice, qui a été pour moi pendant ces 25

dernières années le meilleur père que j'aurais pu souhaiter, et qui m'a poussé à être curieux et

hier auch ganz besonders meiner Tante Jutta danken, die innerhalb von ein paar Tagen die ganze

Einführung durchgelesen und korrigiert hat.

here, please forgive me for this oversight. I am still unsure of how I made it this far, but one thing I know: I would not have made it without you. The words above pale in comparison to what I owe you all, I have written and rewritten them many times and I know I'll never be able to express the feeling appropriately, so all I can do is apologize and say it once more, thank you all so very much. iv

Contents

Acknowledgmentsiii

Abbreviationsxi

I Introduction 11 Placenta5

1.1 Challenges of viviparity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

1.1.1 Maternofetal exchanges . . . . . . . . . . . . . . . . . . . . . . . . . . 5

a. Nutrients 6 b. Oxygen 8 c. Waste 9

1.1.2 Placentation and the maternal immune system . . . . . . . . . . . . . . 9

a. Major histocompatibility complex expression 9 b. Uterine natural killer cells 10 c. Adaptive immunity 11

1.1.3 Maternofetal communication . . . . . . . . . . . . . . . . . . . . . . . 11

a. Placental hormones 11 b. Extracellular vesicles 12

1.2 Mammalian eutherian placentas. . . . . . . . . . . . . . . . . . . . . . . . 13

1.2.1 Origin and evolution of the mammalian placenta . . . . . . . . . . . . 13

a. Monophyletic origin 13 b. Placental diversity 13

1.2.2 Placental types by maternofetal interface . . . . . . . . . . . . . . . . . 16

a. Epitheliochorial placentation 18 b. Synepitheliochorial placentation 20 c. Endotheliochorial placentation 22 d. Hemochorial placentation 22

1.3 Viviparity in non-mammalian species. . . . . . . . . . . . . . . . . . . . . 26

1.3.1 Prevalence of viviparity outside of mammals . . . . . . . . . . . . . . 26

v a. Invertebrates 26 b. Non-mammalian vertebrates 27

1.3.2 Examples of non-mammalian placentas . . . . . . . . . . . . . . . . . 30

a. Non-vertebrates: the placenta of salps 30 b. Fish: placentation in sharks 31 c. Lizards: placentation inMabuyaand other Scincidae 32

2 Retroviruses38

2.1 Exogenous Retroviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

2.1.1 Genomic orgarnisation . . . . . . . . . . . . . . . . . . . . . . . . . . 39

a. Non-coding features 39 b. Gag 41 c. Pro and Pol 42 d. Env 44 e. Regulatory and accessory proteins 44

2.1.2 Retroviral phylogeny . . . . . . . . . . . . . . . . . . . . . . . . . . . 48

a. SubfamilyOrthoretrovirinae48 b. SubfamilySpumaretrovirinae51

2.1.3 Viral cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

a. Viral entry 53 b. Reverse transcription 53 c. Genome integration 57 d. Protein expression 60 e. Assembly and budding 61 f. Maturation 64

2.2 Endogenous Retroviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

2.2.1 Endogenization of retroviral sequences . . . . . . . . . . . . . . . . . . 67

a. Infection of germinal cells 67 b. Intra-genome spreading of ERVs 69 c. Groups of ERVs 71

2.2.2 Impact of retroviral integration on the host . . . . . . . . . . . . . . . . 72

a. LTR integration can drive ectopic gene expression 72 b. Impact of retroviral gene acquisition on host physiology 76

2.2.3 Fate of ERVs and control by the host . . . . . . . . . . . . . . . . . . . 78

a. Epigenetic regulation of ERV expression 78 b. Accumulation of mutations and solo LTR formation 79 c. Exaptation and purifying selection 80

3 Syncytins81

3.1 Retroviral envelopes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

vi

3.1.1 Functional domains . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81

a. Domains of the SU 81 b. Domains of the TM 83

3.1.2 Env induced membrane fusion . . . . . . . . . . . . . . . . . . . . . . 86

a. Implication of the cognate receptor in fusion 86 b. Model of viral fusion protein class I induced membrane fusion 89

3.2 Syncytins in mammals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

3.2.1 Human syncytins: Syncytin-1 and Syncytin-2 . . . . . . . . . . . . . . 90

a. Syncytin-1 92 b. Syncytin-2 94

3.2.2 Mouse syncytins: Syncytin-A and Syncytin-B . . . . . . . . . . . . . . 95

a. Discovery 95 b. Expression in 2 segregated layers 95 c. Impact of Syncytin knockout on placental physiology 96

3.2.3 Other mammalian syncytins . . . . . . . . . . . . . . . . . . . . . . . 98

a. Rabbit: Syncytin-Ory1 98 b. Cat and dog: Syncytin-Car1 99 c. Old world monkey: EnvV2 99 d. Cattle and sheep: Syncytin-Rum1 and Fematrin-1 99 e. Squirrel and marmot: Syncytin-Mar1 100 f. Tenrec: Syncytin-Ten1 100 g. Short-tailed opossum: Syncytin-Opo1 100

3.2.4 Syncytin-like Env . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

a. Conserved ERV Env with placental expression in human 101 b. Non-human syncytin-like genes 102

3.3 Syncytins and evolution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

3.3.1 Ancestral syncytin and syncytin replacement . . . . . . . . . . . . . . 103

a. Example of EnvV2, a decaying syncytin in humans 104 b. Baton pass hypothesis 105

3.3.2 Syncytin diversity and placental diversity . . . . . . . . . . . . . . . . 106

3.3.3 Other roles of syncytins . . . . . . . . . . . . . . . . . . . . . . . . . . 108

a. Cell-cell fusion in muscles 109 b. Osteoclast fusion 109 c. Syncytins and pathologies 110

4 Objectives111

II Results 113vii

1 Implication of ERVenvgenes in non-mammalianMabuyaplacen-

tation114

1.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114

1.2 A syncytin in a placental lizard. . . . . . . . . . . . . . . . . . . . . . . . . 117

2 Implication of ERVenvgenes in placental structural transitions in

Hyaenidae135

2.1 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

2.2 Hyena-specic retroviral envelope gene capture and placenta evolution. . . 139

III Discussion 1671 Two novel Env with a potential placental role and a new SLC1A5 Env168

1.1 Hyena-Env2 is a conserved syncytin-like envelope gene expressed during

hyena placentation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168

1.2 Hyena-Env3 is a member of the SLC1A5 interference group with a peculiar

tropism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

1.3 Syncytin-Mab1: characterization of a non-mammalian syncytin and its re-

ceptor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170

2 Implication of syncytins and syncytin-likes in placental evolution172

2.1 Retroviralinsertionshavebeenaconstantdrivingforceofvertebrateevolution172

2.2 Syncytin-Mab1 and convergent evolution of animal placentas. . . . . . . . 174

2.2.1 Convergent use of ERVenvgenes in placentation . . . . . . . . . . . . 174

2.2.2 Syncytin-Mab1 as the rst example of a founding syncytin . . . . . . . 175

2.3 Syncytins and syncytin-likes and divergent evolution of the mammalian

placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175

3 Syncytin-likes and alternative envelope functions in the placenta178

3.1 Growing evidence of conservation of non-fusogenic Env. . . . . . . . . . . 178

3.2 Alternative placental roles for Env. . . . . . . . . . . . . . . . . . . . . . . 178

3.2.1 Immunosuppression . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178

3.2.2 Dierentiation and proliferation . . . . . . . . . . . . . . . . . . . . . 180

3.2.3 Invasion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180

3.3 Syncytin-likes in epitheliochorial placentation. . . . . . . . . . . . . . . . . 183

4 Conclusion185

viii

IV Bibliography 187

V Résumé Français 223

List of Figures

1 Dynamics of placental glucose and amino-acid transport . . . . . . . . . . . . 7

2 Timed tree of major mammalian clades. . . . . . . . . . . . . . . . . . . . . . 14

3 Diversity of eutherian placentas . . . . . . . . . . . . . . . . . . . . . . . . . . 17

4 Types of maternofetal interface in eutherians . . . . . . . . . . . . . . . . . . . 19

5 Heterologous syncytium formation in ruminant placentas . . . . . . . . . . . . 21

6 Remodeling of maternal blood vessels by extravillous trophoblast cells in humans 24

7 Matrotrophy in Animalia clades . . . . . . . . . . . . . . . . . . . . . . . . . . 28

8Mabuyaplacental structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

9 Organization of retroviral virions and genomes . . . . . . . . . . . . . . . . . . 40

10 Organization of the complex HIV-1 genome . . . . . . . . . . . . . . . . . . . 45

11 Phylogeny of retroviral genera based on RT or TM analysis . . . . . . . . . . . 49

12 Retroviral replication cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

13 Reverse transcription . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

14 Retroviral genome integration . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

15 Model of ESCRT mediated viral budding . . . . . . . . . . . . . . . . . . . . 64

16 Retroviral maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

17 Retroviral endogenization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

18 ERV amplication and fate . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

19 ERV family representation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72

20 LTR insertional mutagenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . 74

21 Detailed structure of Env . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

22 Sequence of the ISD and CX

nC1-2motif and rationale of the mice immunosup- pression assay . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85

23 Retroviral Env mediated cell fusion . . . . . . . . . . . . . . . . . . . . . . . . 86

24 Nature of retroviral receptors and SLC1A5 RBD . . . . . . . . . . . . . . . . . 88

25 Phylogeny of mammals with known syncytins positioned . . . . . . . . . . . . 91

26 Impact of syncytin KO in mice . . . . . . . . . . . . . . . . . . . . . . . . . . 97

ix

27 Compared evolutionary fates of HERV-W Env and EnvV2 in simians . . . . . . 104

28 Phylogeny of retroviral syncytins among retroviral genera based on RT or TM

analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107

29 Dierences in syncytin transcript initiation . . . . . . . . . . . . . . . . . . . . 108

1 Phylogeny of mammals with emphasis on carnivorans . . . . . . . . . . . . . . 143

2 Characterization of the identiedCrocuta crocutaenvelope candidates . . . . . 145

3 Entry date and conservation of env genes in Carnivora . . . . . . . . . . . . . . 147

4 Alignment of Hyena-Env2 genes from all four extant hyena species . . . . . . . 148

5Hyena-Env2associated provirus and its genomic location . . . . . . . . . . . . 150

6 TheHyena-Env2associated virus is a gammaretrovirus . . . . . . . . . . . . . 151

7 Comparison of carnivoran and hyena placentas . . . . . . . . . . . . . . . . . . 153

8 Expression pattern ofsyncytin-Car1andHyena-Env2. . . . . . . . . . . . . . 154

9 Fusogenicity assay for the three hyena envelope proteins . . . . . . . . . . . . . 155

10 Viral titers obtained in the pseudotyping assay using all three hyena envelopes . 156

11 Hyena-Env3 belongs to the SLC1A5 interference group of envelopes . . . . . . 158

x

Abbreviations

APC:antigen presenting cell

ALV:avian leukosis virus

BaEV:baboon endogenous virus

BLV:bovine leukemia virus

BNC:binucleate cell

CA:capsid protein

CCD:catalytic core domain

CT:cytotrophoblast

CTD:C-terminal domain

EIAV:equine infection anemia virus

enJSRV:endogenous Jaagsiekte sheep retrovirus

Env:envelope

ER:endoplasmic reticulum

ERV:endogenous retrovirus

ESCRT:endosomal sorting complex required for transport

ETn:early transposon

EVT:extravillous trophoblast

FLV:feline leukemia virus

Gag:group-specic antigen

GaLV:gibbon ape leukemia virus

GCMa:chorion-specic transcription factor GCMa

xi

HA:hemagglutinin

HBZ:HTLV-1 basic zipper factor

HEMO:human endogenous MER34 (medium re-iteration family 34) ORF

HERV:human endogenous retrovirus

HIV:human immunodeciency virus

HLA:human leukocyte antigen

hPL:human placental lactogen

HR:heptad repeat

HTLV:human T-lymphotropic virus

IAP:intra-cisternal A-type particle

IAPE:IAP-related retroviral element containing anenvgene ICTV:International Committee on Taxonomy of Viruses

IN:integrase

ITIM:immunoreceptor tyrosin-based inhibitory motif

JSRV:Jaagsiekte sheep retrovirus

KoRV:koala retrovirus

KRAB-ZFP:Krüppel associated box zinc nger proteins

LTR:long terminal repeat

Ly6E:lymphocyte antigen 6E

MA:matrix protein

MFSD2A:major facilitator superfamily domain containing 2 A

MHC:major histocompatibility complex

MHR:major homology region

MLV:murine leukemia virus

MMTV:mouse mammary tumor virus

xii

MPMV:Mason-Pzer monkey virus

MPZL1:myelin protein zero-like 1

My:million years

Mya:million years ago

NAHR:non-allelic homologous recombination

NC:nucleocapsid protein

Nef:negative factor

NK:natural killer

NTD:N-terminal domain

ORF:open reading frame

PBS:primer binding site

PIC:pre-integration complex

Pol:polymerase

PPT:polypurine tract

Pro:protease

PRR:proline-rich region

PtdIns(4,5)P

2:phosphatidylinositol-4,5-biphosphate

PTLV:primate T-lymphotropic virus

RDR:RD114 and D-type receptor

Rev:regulator of expression of viral proteins

Rex:Rev homolog

RSV:Rous sarcoma virus

RT:reverse transcriptase

RTC:reverse transcription complex

SFV:simian foamy virus

xiii

SIV:simian immunodeciency virus

SLC:solute carrier

ST:syncytiotrophoblast

SU :surface subunit

Tat :trans-activator

Tax :trans-activating regulatory protein

TM :transmembrane subunit

TSD:target site duplication

uNK:uterine natural killer

UTR:untranslated region

Vif:viral infectivity factor

Vpr:viral protein r

Vpu:viral protein u

WDSV:walleye dermal sarcoma virus

xiv

Part I

Introduction

1 2 The eld of virology is a relatively new one: less than two centuries ago the notion of a existence.Years afterthesespeculations,Chamberlandinvented hisfamouslter,able toremove even bacteria from a solution passed through it. It was this discovery that enabled Beijerinck in

1898 to show that ltered sap from plants infected with what is now known as tobacco mosaic

virus was able to infect other plants. He concluded from this that the causative pathogen was smaller than a bacteria and called it a virus. From there virology advanced in leaps and bounds and in the following decades a great number of viruses were identied and linked to diverse diseases. In 1911 Rous published his discovery of what would later become known as Rous sarcoma virus (RSV, Rous, 1911). While this was not the rst retrovirus to be discovered, and while Rous himself did not know about the true nature of the infectious agent he described, this discovery would lead to the creation of both the elds of tumor viruses and retrovirology. In the 1960s, cancers caused by RSV in egg-laying hens were becoming an ever more important problem, leading to many new investigations into the characteristics and behavior of the virus. In 1961 Crawford & Crawford (1961) isolated the virus on a density gradient and determined that it had an RNA genome. Further research in the following years, making use of Mendelian genetics,

both in live chicken and in infected cells, suggested that the viral genes could be stably inherited,

which would imply that they had become part of the genome. This posed a major problem since at the time the "central dogma of biology" postulated that DNA could be transcribed into RNA, but that the opposite was impossible. How then could an RNA virus integrate its genes into a DNA genome? Nevertheless, in 1964 Temin introduced the provirus hypothesis, coining this term in the context of eukaryote viruses, and postulating that RSV could convert its RNA genome into a DNA genome which could then be inserted into the host genome (Temin,

1964). This hypothesis proved unpopular until the discovery 6 years later of reverse transciptase

(RT, Baltimore, 1970; Temin & Mizutani, 1970), which nally delivered the key element: an enzyme able to convert RNA information into DNA information, and which led to the naming and creation of the Retroviridae family by the International Committee on Taxonomy of Viruses in 1975 (ICTV, 1975). Since viral replication of members of this family necessitates integration into the host 3 genome, endogenous retroviruses (ERV) were discovered in parallel with the family itself, rst in chicken and mice and later in humans and other vertebrates. The identication of retroviral sequences that were an integral part of host genomes (sequencing of the human genome later revealed that ERVs represent 8% of the genome Lander et al., 2001) led to the search for the function of these elements, and a number of them have been identied as protecting their host from infection by exogenous retroviruses. A role not linked to viral infection, and probably the most remarkable example of ERV function, is the exaptation ofsyncytinsin mammals. The rst placenta (Blond et al., 2000; Mi et al., 2000). Since then numerous othersyncytinshave been identied in other mammalian placentas and their role in trophoblast fusion has been conrmed using KO mice. To delve further into these topics, I will rst discuss the characteristics of mammalian and non-mammalian placentas, a pre-requisite for discussion ofsyncytinrole and acquisition. I will then present retroviruses in greater detail and nally I will talk specically about captured envelope genes, especiallysyncytins. 4

1. Placenta

sions during vertebrate evolution (Blackburn, 2015), most famously in Eutherians. In viviparous species, by denition, the embryo is not exposed to the external environment and the exchanges necessary for embryonic development must take place between the embryo and the mother. These exchanges are rendered possible by the placenta. The placenta is a highly variable organ, both in structure and functionality. Its simplest denition was given by Mossman in his seminal

1937 work on mammalian placentas: "an apposition or fusion of the fetal membranes to the

uterine mucosa for physiological exchange" (Mossman, 1937). This denition encompasses two related notions: the placenta joins maternal and fetal tissues, and it forms an exchange interface between mother and fetus.

1.1 Challenges of viviparity

1.1.1 Maternofetal exchanges

The rst major challenge facing viviparous species is for the mother to act as the go-between of the embryo and the exterior. This means that the mother must not only provide the substances required for embryo development but also that all embryonic waste products must be taken up by the mother and eliminated. The importance of these exchanges during development is very variable depending on the species (Blackburn, 2015). In some cases, the embryo obtains most nutrients from its own yolk and is reliant on the mother mostly for gas and water exchanges, in others the embryo also needs to acquire almost all nutrients necessary for development. These two extremes are called lecithotrophy and matrotrophy, respectively, and form the two ends of a continuum of reproductive strategies that dier by the degree of implication of the mother and the functional capacities of the placenta (Blackburn, 2015). Of note, while almost all oviparous species are by necessity lecithotrophic, the mammalian monotremes (platypus and echidnas) with a 3 mm diameter yolk which takes up maternal nutrients before oviposition, to reach a nal diameter of 17 mm (Hughes, 1993). While this is mentioned here for completeness, "oviparity" will refer to the much more common lecithotrophic oviparous mode of reproduction from here classication of vertebrate reproductive strategies into four major categories, see Table 1. 5 ?. Placenta type are not exhaustive. Adapted from Blackburn (2015).oviparity lecithotrophy matrotrophyviviparity lecitotrophic oviparity: all birds and crocodilians, most squamates, teleosts, some chondrichtyanslecitotrophic viviparity: many squamates, some teleosts, chondrichtyans matrotrophic viviparity: all eutherians and marsulpials, several teleosts and chondrichtyans, a few clades of squamatesmatrotrophic oviparity:

only monotremesSince most of our species of interest will be matrotrophic viviparous, the description of

placental characteristics will focus on this subgroup, however even within this group placental structures show a great amount of variability (see 1.2.1.b.). a. Nutrients In matrotrophic placentation, nutrients that must be supplied to the embryo include carbohy- drates, most amino-acids, fatty acids and metal ions. In mammals, glucose is one of the most important fetal nutrients, providing much of the energy required during fetal growth (Wooding & Burton, 2008, chap. 2). In eutherians, maternal glycemia is higher than fetal glycemia, es- tablishing a concentration gradient that induces glucose transport from the mother to the fetus. In order to transfer the necessary amount of glucose from maternal to fetal blood, diusion is facilitated using glucose transporters (glucose transporter type 1 in all mammalian placentas and additionally type 3 in some, like rat, horse and ewe, see Wooding & Burton, 2008, chap. 2).quotesdbs_dbs6.pdfusesText_11

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