REPRODUCTIONREVIEW

The evolution of the placenta

R Michael Roberts1,2, Jonathan A Green2 and Laura C Schulz3 1C.S. Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA, 2Division of Animal Sciences, University of Missouri, Columbia, Missouri, USA, and 3Department of Obstetrics, Gynecology and Women’s Health, University of Missouri School of Medicine, Columbia, Missouri, USA Correspondence should be addressed to R M Roberts; Email: [email protected]

Abstract

The very apt definition of a placenta is coined by Mossman, namely apposition or fusion of the fetal membranes to the uterine mucosa for physiological exchange. As such, it is a specialized organ whose purpose is to provide continuing support to the developing young. By this definition, placentas have evolved within every vertebrate class other than birds. They have evolved on multiple occasions, often within quite narrow taxonomic groups. As the placenta and the maternal system associate more intimately, such that the conceptus relies extensively on maternal support, the relationship leads to increased conflict that drives adaptive changes on both sides. The story of vertebrate placentation, therefore, is one of convergent evolution at both the macromolecular and molecular levels. In this short review, we first describe the emergence of placental-like structures in nonmammalian vertebrates and then transition to mammals themselves. We close the review by discussing the mechanisms that might have favored diversity and hence evolution of the morphology and physiology of the placentas of eutherian mammals. Reproduction (2016) 152 R179–R189

Introduction It is a specialized organ whose purpose is to provide continuing support to the developing young through the Viviparity has evolved independently and seemingly provision of water, nutrients and gases, and to regulate on multiple occasions across a diverse array of animal maternal–fetal interactions often through hormone groups, including invertebrates (Kalinka 2015). It is production. By this definition, placentas have evolved a phenomenon whereby developing embryos are within every vertebrate class other than birds. Although retained within the reproductive tract, leading to release placentation arose once in the common ancestor of of live offspring as an alternative to the more fecund mammals, it has arisen independently multiple times egg laying or spawning. One consequence of viviparity within other classes, and even families. The story of is that the retained, fertilized egg must either survive off vertebrate placentation, therefore, is one of convergent its own reserves, usually yolk, or obtain some or part of evolution at both the macromolecular and molecular these resources from the mother. The latter situation, of levels. In this short review of placental evolution, we necessity, is expected to lead to increased conflict over first describe the emergence of placental-like structures how provisions are partitioned between the supplier in nonmammalian vertebrates and then transition and the recipient, thus potentially sparking a genetic to mammals themselves. We close the review by arms race. In turn, such conflict is expected to drive discussing mechanisms that might have favored diversity adaptive changes that lead to a more intimate and and hence evolution of the morphology and physiology possibly more felicitous relationship between offspring of the placentas of eutherian mammals. Of necessity, and the reproductive tract of the mother that favors the many important references cannot be cited in a short transmission of both maternal and paternal genes to review of this kind. Instead, we have attempted to direct the next generation, despite a loss of overall fecundity. the reader to scholarly articles that do list the primary The transition from oviparity to viviparity and the source material. subsequent emergence of placentation within some vertebrate taxa clearly required major changes in the morphology and physiology of the reproductive tract Nonmammalian vertebrates and has its origins well before the advent of mammals Cartilaginous fish (Van Dyke et al. 2014, Blackburn 2015). A placenta, as defined originally by Mossman, is the ‘apposition Viviparity is the most common mode of reproduction or fusion of the fetal membranes to the uterine mucosa in elasmobranchs. However, there is a wide range in for physiological exchange’ (Burton & Jauniaux 2015). the degree of maternal provisioning of the embryo after

© 2016 Society for Reproduction and Fertility DOI: 10.1530/REP-16-0325 ISSN 1470–1626 (paper) 1741–7899 (online) Online version via www.reproduction-online.org Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access

10.1530/REP-16-0325 R180 R M Roberts and others ovulation (Wourms & Lombardi 1992), with embryos Amphibians of some species depending entirely on the yolk sac for Viviparity has arisen multiple times in amphibians, all of pregnancy, e.g. the spiny dogfish, which at birth accompanied in some cases with the evolution of weighs 40% less than the yolk-filled fertilized egg from placentas. In frogs, there are examples in which the which it develops. The tiger shark, by contrast, solves tadpoles develop in the father’s mouth, in the mother’s such limiting provisioning; in which the dominant stomach, or on the skin of the back (Wake 1993). In embryo eats all of its littermates and any unfertilized the marsupial frogs, development occurs inside a eggs before birth (Korsgaard & Weber 1989). specialized maternal pouch on the back of the animal. In the elasmobranchs, two placental types are Following ovulation, secretory cells of the vascularized observed. Among stingrays, finger-like projections pouch enlarge. The pouch epithelium is closely apposed of the uterine wall, termed trophonemata, provide to specialized fetal gills, allowing exchange between histotrophic nutrition to the developing embryo maternal and fetal circulations (Savage 2002). This, as (Hamlett et al. 1993), while the epithelium overlying A.M. Carter wrote, ‘would satisfy most people’s definition uterine blood vessels thins, lessening the barrier to of a placenta’ (Carter 2016). Arguably, however, a exchange. The mature embryo of the cownose ray, for structure found outside the reproductive tract, especially example, weighs 3000 times as much as the egg as a following external fertilization that occurs in these frogs result of reliance on the mother rather than the egg and the sea horses described earlier, does not fit the yolk (Hamlett et al. 1993). A different placental type, typical definition of a placenta. Nor have any of the ‘gill the yolk sac placenta, has evolved multiple times placentas’ of these endangered frog species yet been in the ground sharks (Wourms & Lombardi 1992). shown to be the primary source of fetal nutrient support. After the yolk has been consumed, the yolk sac becomes modified into an umbilical cord region and a placental region (Hamlett et al. 1993), which Reptiles become closely apposed to the epithelium of a highly vascularized oviduct. Viviparity occurs in more than 25 families of lizards and snakes (squamate reptiles). Although estimated Teleosts by some to have arisen independently more than one hundred times, it is conceivable that there was a single In Poeciliopsis fish, eggs are retained within the origin of viviparity and multiple subsequent reversions follicle after fertilization and throughout embryonic to oviparity (Pyron & Burbrink 2014, Van Dyke et al. development (Wourms & Lombardi 1992). Most species 2014, Blackburn 2015). In many species, the embryo are lecithotrophic, relying on yolk, but in others, a highly relies on egg contents for nutrition, but in others a folded, follicular epithelium forms a ‘follicular placenta’ range of adaptations of the female reproductive tract with the embryonic pericardial sac. This epithelial layer provides a means to exchange gases and nutrients is lined with microvilli, while the surrounding tissue is with the conceptus (Stewart 2015). In squamates the highly vascularized, presumably to facilitate maternal– placenta is chorioallantoic, but unlike mammals it fetal exchange (Kwan et al. 2015). This type of placental does not develop from an early arising, extraembryonic structure has arisen several times during Poeciliopsis trophoblast layer. Most squamate placentas demonstrate evolution (Kwan et al. 2015) and has been subsequently a simple interdigitation of the chorioallantois with the lost and regained many times, making it a model for the uterine epithelium (Stewart 2015), but in some skinks evolution of placentation (Pollux et al. 2014). the interface is more intimate (Fig. 1). In the case of Among syngnathid fish (pipefish and seahorses) the the African skink Trachylepis ivensi, there is even a males, and not the females, become pregnant, after the degree of invasive implantation, with direct contact female transfers the fertilized eggs to a brood pouch between chorionic projections and maternal capillary on the ventral side of either the trunk (Gastrophori) or endothelium (Blackburn & Flemming 2012). the tail (Urophori) of the male’s body. The degree of The chorioallantoic placenta of viviparous lizards can contact and exchange between developing embryos be highly efficient in facilitating exchange of nutrients and the father range from minimal to situations that and gases. Offspring of the Mabuya lizard weigh display all the defining features of placentation Wilson( 500 times more at birth than the egg at fertilization, et al. 2001). For example, in the straight-nosed pipe fish indicating a nearly complete reliance for growth on Nerophis ophidion, eggs stick to the epithelium of the maternally supplied materials (Thompson & Speake father’s pouch, which is open to the sea environment 2002). There is also evidence for the expression of active (Carcupino et al. 2002), while in the pot-bellied transporters at the sites of maternal–fetal apposition in seahorse Hippocampus abdominalis, the pouch is some species (Murphy et al. 2011) and for placental sealed and its epithelium highly folded, thinned and production of steroid hormones (Painter & Moore 2005). vascularized (Carcupino et al. 2002), thereby allowing Overall, where placentation occurs in squamates, it exchange of nutrients. bears a superficial resemblance to the epitheliochorial

Reproduction (2016) 152 R179–R189 www.reproduction-online.org

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access The evolution of the placenta R181

Figure 1 Viviparity in reptiles: (A) Drawing from a section of the mature chorioallantoic placenta of the Australian skink Egernia cunninghami carrying developing young, showing the maternal capillaries closely adjoining the allantoic capillaries on the fetal side. (B) Drawing from a section of the immature chorioallantoic placenta of the Australian skink Egernia entrecasteaux. The section illustrates the folded placental face likely involved in releasing histotrophic material that can be taken up by the chorionic ectoderm. Also, note the close apposition of maternal blood capillaries with the epithelium of the reproductive tract. The diagrams are based on Fig. 15.5 and 15.7 from E.C. Amoroso’s review on placentation (Amoroso 1952), which were redrawn from Weekes (1935). placentation encountered in some eutherian mammals cell layer, with trophoblast materializing from the pole and carries out many of the same functions, but its of the blastocyst opposite the position of the future formation does not involve the formation of a trophoblast embryo (Frankenberg et al. 2013, Morrison et al. 2013, lineage, a feature unique to placental mammals. Familari et al. 2016). There are also indications that early lineage specification may be controlled by a similar set of transcription factors as in eutherians (Frankenberg Mammals et al. 2013, Morrison et al. 2013, Familari et al. 2016). All mammals except the egg-laying platypus and the five The trophoblast cells originating from the marsupial species of echidnas, the only surviving monotremes, rely blastocyst combine with the yolk sac endoderm on a placenta for their reproduction. Indeed, the first and extraembryonic mesoderm to form a yolk sac lineage decision made during embryonic development placenta, which can be bi- or trilaminar (Renfree 2010). of Mammalia is the segregation of cells that are destined However, there are a species of koalas, wombats and to become the external tissue layer of the placenta. This bandicoots, in which a chorioallantoic placenta forms, lineage, usually called trophoblast (or, because it forms but it appears to be supplementary to the main yolk sac the exterior of the conceptus, trophectoderm), diverges placenta (Freyer et al. 2003). Although the placentas early from the pluripotent lineage that advances to of marsupials are generally regarded as noninvasive form the inner cell mass. The cells that give rise to the and of the epitheliochorial type (see next section), an hypoblast and epiblast are unique to mammals. The area of syncytium forms in the yolk sac placenta of the term trophoblast was first coined by Hubrecht (1904). Its gray short-tailed opossum and possibly related species. roots are ‘tropho’ meaning nourishment, and ‘blast’ for This tissue makes direct contact with maternal blood embryonic. It is therefore questionable whether embryo- vessels (Zeller & Freyer 2001). Additionally, trophoblast derived placental cells of other animals, which unlike syncytialization (syncytial trophoblast; STB), where mammals do not form an initiating trophectoderm, adjacent cells fuse to produce cells with more than a should be termed ‘trophoblast’, despite many of their single nucleus, is accompanied by the expression of shared functions. When and how trophoblast emerged an endogenous, retrovirus-derived protein, analogous in the presumed metatherian ancestors of the Class to what occurs in many eutherians (Cornelis et al. Mammalia is mysterious and unlikely ever to be revealed 2014). Another similarity to the eutherians is that the from the fossil record. placenta of the tammar wallaby secretes a complement of hormones that include IGF2 and relaxin, which, in that species, may be responsible for the phenomenon of Marsupials maternal recognition of pregnancy (Renfree 2010). Although eutherians are often referred to as ‘placental mammals’, marsupials do possess placentas. However, Eutherians the placentas are short-lived and marsupials give birth to relatively underdeveloped young. In marsupial Origin of trophoblast: Eutherians consist over 5000 blastocyst, blastomeres adhere to the inner surface of the species in roughly 20 phylogenetic orders. Most of zona pellucida, resulting first in a cup-shaped blastocyst, our knowledge about their early development and the and then a hollow sphere with no discernible inner cell events that lead to the initial specification of trophoblast mass (Selwood & Johnson 2006). Both the embryonic has been obtained only in a handful of these species, and extraembryonic lineages emerge from this single especially the mouse. In mouse (Mus musculus), the www.reproduction-online.org Reproduction (2016) 152 R179–R189

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access R182 R M Roberts and others first visible differentiation event, called compaction, example, placentas come in a range of shapes and sizes, occurs between the 8 and 16 cell stage of embryonic and have been placed in groups based on the general development, when the blastomeres polarize to form gross morphologies of the sites where the chorion extended contact zones with their neighbors and an attaches to the endometrium (Fig. 2). They have also been outward-facing apical surface (Posfai et al. 2014). classified according to how many cell layers separate Further symmetrical and asymmetrical divisions follow, the maternal and fetal circulations (Fig. 2). A simplified so that by the 16 cell morula stage a population of version of this system recognizes three main placental polarized cells exist on the cell surface, which becomes types (Renfree 1982): epitheliochorial, in which there is trophectoderm, and another population of cells are no erosion of the uterine epithelium; endotheliochorial, positioned inside, which is the precursor of the inner cell where the invading trophoblast reaches but does not mass (ICM). By the time of blastocyst formation, when penetrate maternal capillaries within the endometrium; the mouse conceptus comprises about 32 cells, about and hemochorial, where the trophoblast surface is in two-thirds of which are trophectoderm, the precursors direct contact with maternal blood (Fig. 3). A fourth of extraembryonic endoderm (hypoblast) have begun to type, synepitheliochorial, has been recently used to segregate toward the base of the ICM. From this location, describe the placentas of ruminants (Wooding 1992). they migrate outward to line the trophectoderm, Here, specialized trophoblast binucleated cells fuse forming the yolk sac cavity. Later, extraembryonic with uterine epithelial cells to form trinucleated cells, mesoderm joins with the trophectoderm to form what a syncytium, or both. The placentas of ruminants, with at this stage is a bilayered chorion. Although there are the exception of the phylogenetically more primitive clear morphological similarities in the steps leading to tragulids, are also characterized as cotyledonary blastocyst formation in rodents, humans and domestic (Fig. 2). Cotyledons are the primary sites of attachment mammalian species, there are differences in how of the chorion to the endometrium and comprise tufts these events are timed and subsequently played out. In of villous trophoblast that interdigitate and interlock many species, for example, mesoderm differentiates to with complementary structures on the endometrium, vascularize the yolk sac, forming a yolk sac placenta that called caruncles. It is within these sites, often known is eventually replaced by the chorioallantoic placenta. as placentomes, that binucleated cells, placental and Such a placenta does not form in humans, but persists maternal blood capillaries, and placental interchange to term in rodents and lagomorphs. Similarly, compared are most concentrated. Therefore, this kind of placenta is with the mouse, conceptuses from many species undergo a derived form, secondary to the more superficial, diffuse at least one further round of cell division before the epitheliochorial type typical of most other artiodactyls. blastocoel cavity becomes visible. For details on how Superficial vs invasive placentation: Intuitively, placentas subsequently develop and begin to diverge in it might be inferred that the least invasive types of morphology, the reader is directed to the still germane placenta, the kind where multiple cell layers separate reviews by Amoroso (1952) and Renfree (1982). the two blood supplies (Fig. 2B), would be the most Range of placental morphologies: Despite the inefficient and also the most primitive of all placental spectacular diversity encountered in placental structure types because there are more apparent physical barriers at both the gross and microanatomical levels (Enders & to limit the movement of nutrients and dissolved gases. Carter 2004), there have been attempts over the years Also, such placentas have a resemblance to placentas to classify placentas and (somewhat unsuccessfully) described earlier for nonmammalian species, such as to relate the outcomes to mammalian phylogeny. For skinks (Fig. 3). However, this is clearly not the case

Figure 2 Cartoon illustrating the diversity of placental morphologies encountered in placental mammals.

Reproduction (2016) 152 R179–R189 www.reproduction-online.org

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access The evolution of the placenta R183

Figure 3 Cartoon indicating how placentas can be classified according to the numbers and kinds of cell layers that separate the bloodstreams of the mother and conceptus.

(Wildman et al. 2006). Compare, for example, the employed, namely the delivery of these components not relative maturity and independence of a newborn horse, in the blood but in uterine secretions – a process called pig or whale, supported during their gestations by diffuse histotrophic nutrition (Fig. 5C) (Renegar et al. 1982). epitheliochorial placentas, to a hapless pup born to a The uterine glands of the pig, for example, release mouse or a baby born to a human, species where the uteroferrin, a bi-iron containing acid phosphatase to placenta is hemochorial and discoid. Nor is the more supply iron. Uteroferrin and other proteins with a similar superficial form of placenta evolutionarily more ancient provisioning function are taken up by specialized than the kinds that are invasive and make direct contact regions of endocytic trophoblast cells congregated with maternal blood. On the contrary, careful analyses, in cup-like structures called areolae, which develop in which placental features were mapped to mammalian opposite the mouths of each uterine gland (Fig. 5C). phylogenies, have clearly dispelled this myth and From there, the maternal factors are transported via demonstrated that the epitheliochorial placenta is the fetal bloodstream to the liver and other organs for not only a derived form that has evolved from a more processes such as hematopoiesis (Renegar et al. 1982). invasive placental type, but has arisen independently in The likely advantages of a noninvasive placenta over the three distinct mammalian lineages, including primates (Wildman et al. 2006) (Fig. 4). Moreover, this and similar trees based on other features of the placenta strongly imply that the placenta of the last common eutherian ancestor was discoid, either hemochorial or endotheliochorial (Mess & Carter 2007), and possessed a labyrinth-type of placental interdigitation. It should be stressed that the perceived disadvantages of extended diffusion distances for dissolved gases and solutes encountered with a superficial placenta, like that of the pig, are largely illusory. As pregnancy proceeds, the surfaces of the uterine and trophoblast epithelial layers become interlocked (Fig. 5B). Capillaries on the maternal and fetal sides come within a few microns of each other (Fig. 5A), often squeezing down to the tight junctions between the trophoblast cells on the one side and uterine epithelial cells on the other, probably Figure 4 The evolution of the placental interface in terms of degree of allowing efficient exchange of small molecules (Friess invasiveness of the placental tissue into maternal tissue, with et al. 1980). Movement of macromolecules that carry epitheliochorial being the least invasive and hemochorial being most essential components such as metals and vitamins is invasive. From Fig. 2 of Wildman et al. (2006), with permission; more problematic, but an alternative strategy has been Copyright (2006) National Academy of Sciences, USA. www.reproduction-online.org Reproduction (2016) 152 R179–R189

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access R184 R M Roberts and others

Figure 5 The porcine placenta: (A) Fetal capillaries (FC) at day 58 of pregnancy protrude deeply into the trophoblast, with the diffusion distance between fetal bloodstream and maternal uterine epithelium (UE) reduced to a few micrometers; (B) At day 110 of pregnancy maternal capillaries (MC) project between uterine epithelial cells, bringing the maternal and fetal capillaries within 3–5 μM; (C) At day 30 of pregnancy, the microvilli on the trophoblast surface (TR) interdigitate with the ones on the uterine epithelium (UE) to provide an intimate contact layer. Maternal capillaries (MC) are placed just below the basal lamina of the UE; (D) A general view of a dome-shaped areola (AE) situated above the mouth of a uterine gland (UG) at day 30 of pregnancy. Figure 5A–C are from Friess et al. (1980); Fig. 5D is from Friess et al. (1981) with permission. more primitive hemochorial and endotheliochorial types et al. 1996). In ruminant species, the pregnant mother include reduced exposure to the potential threats of the responds to the presence of the conceptus even before maternal immune system, less damage to the uterus the trophoblast has attached to the uterine wall. The associated with birth and elimination of the placenta, factor responsible is not a gonadotropin, but instead and minimizing the transmission of fetal cells into the a type 1 interferon-τ (IFNT), which acts on the uterine maternal blood circulation and vice versa. Finally, epithelium, where it modulates the release of the superficial placentation may limit disease transmission luteolytic factor, prostaglandin F2α, that would normally between fetus and mother. cause the corpus luteum to regress (Bazer et al. 1997, As the nature of the maternal–fetal interface evolves, Roberts et al. 1999). In pig, where maternal recognition so does the nature of the biochemical communication of pregnancy is also achieved during the period when possible between conceptus and mother. This is the conceptuses are elongating within the uterine lumen, particularly true in early pregnancy where there is an the anti-luteolytic factor appears not to be a protein, urgency to interrupt estrous cyclicity and maintain but the steroid hormone estrogen (Spencer et al. 2007). continued production of progesterone, if the pregnancy Selective mechanisms that may contribute to placental is to continue (Bazer et al. 2009). As far as is known, diversity: It is generally recognized that there are it is invariably the trophoblast that is responsible for additional driving forces promoting adaptive changes generating this signal for maternal recognition of in the placenta and hence contributing to its rapid pregnancy, although the process is understood in only a evolution. One is undoubtedly the struggle for control handful of species and even then rather poorly. What is of maternal physiology in terms of nutrient allocation clear is that the mechanisms are highly variable, evolving (Fowden & Constancia 2012). As the demands of the rapidly, and no one approach is used widely across taxa. fetus increase, they will likely conflict with the ability A couple of examples illustrate the kind of strategies of the mother to provide such resources. An extensive used in apes, where implantation occurs immediately literature has developed around this topic, with after the blastocyst attaches, and in artiodactyls, where particular emphasis on the role played by imprinted implantation is superficial and delayed. In the human and genes in controlling nutrient supply and growth of the most probably higher primates, but not in strepsirrhines fetus (Reik et al. 2003). Many placental gene products, (lemurs and related species) that have a noninvasive including hormones and transporters, for example, likely trophoblast, chorionic gonadotrophin (CG) provides play a role in raising the concentrations of nutrients luteotropic support to the progesterone-producing cells in maternal blood and facilitating their uptake by the of the corpus luteum soon after implantation. In women, placenta. There is, thus, a drive to keep the paternal hCG becomes measurable in blood and even in urine genes representing the fetus active, while silencing by the second week of pregnancy, most likely as a result the corresponding maternal alleles. Maternal efforts to of being released directly into maternal capillaries even counteract the acquisitiveness of the fetus may lead to before the villous placental bed has formed (Roberts the evolution of oppositely imprinted genes. Again, most

Reproduction (2016) 152 R179–R189 www.reproduction-online.org

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access The evolution of the placenta R185 speculation on the role of imprinted genes has come the duplicated genes to acquire new functions, and, from the mouse, with roles inferred for the human, both through the acquisition or loss of regulatory regions, species with an invasive placenta (Reik et al. 2003). Very changes in the temporal, spatial, or magnitude of little is known about imprinting in those species where transcription compared with the original gene. Gene there is little or no direct access of the trophoblast to family expansions associated with distinct placental maternal blood, although data are beginning to emerge types have arisen repeatedly in eutherians (Rawn & (Chen et al. 2016). Cross 2008). Here, we provide four examples from the A second force driving placental evolution is many known placenta-specific gene families. In general, undoubtedly the avoidance of immune rejection assigning function of individual members within a family (Hemberger 2013), a process still little understood, will be difficult. Indeed, knockouts in mice performed although speculation abounds. It is assumed that to on single members of gene families have generally not minimize attention from various arms of the maternal been informative, possibly because phenotype is not immune system, the trophoblast must continue to obviously impaired within the friendly confines of a evolve counter-measures for its own protection and even vivarium, although it may become so when the pregnant advantage. These measures will undoubtedly be subtle animal is under stress (Ain et al. 2004). Also, products and complex and change as the degree of intimacy with of multigene families likely overlap in function, so that maternal system itself evolves. Some clues may emerge loss of one gene may be compensated by the presence by examining candidates encoded by rapidly evolving of one or more of its orthologs. Finally, family members genes and gene families within individual mammalian may even interact in an epistatic manner, providing a clades, some of which are discussed in the next section. combinatorial benefit not achieved by a single member operating alone. The growth hormone and prolactin-related proteins Evolution of placenta-specific genes are found in primates, rodents and ruminants and, most Despite the observation that the initial lineage likely, other taxa. Interestingly, gene family expansions regulators for trophoblast cell fate decisions may be at have occurred independently in these different lineages, least partially conserved across mammals, the resulting providing yet another example of convergent evolution. placental structures and their associated trophoblast Growth hormone (GH) and prolactin (PRL) themselves cell populations appear not to be governed by arose from a common ancestral gene. In most species, particular master genes. There are a few coding genes, the GH gene is a single copy, but in humans, there e.g., GCM1, a transcription factor that plays a role are five members, one restricted in expression to the in controlling the formation of syncytial trophoblast pituitary and the other four to the placenta (Haig 2008). (STB) (Cross et al. 2003) that appear to have an entirely Their likely role is in resource allocation between the placental function in the sense that they have not fetus and the mother. By contrast, there is only a single been implicated in developmental events outside the copy of the PRL gene in human, whereas there are 23 trophoblast lineage. However, it seems likely that much members in mouse, 24 in rat and 12 in cattle (Haig of the structural diversity and functional refinements 1993). All except prolactin itself are expressed in associated with mammalian placentas depend on the placenta. In mouse, they have diverse patterns of widely expressed transcription factors operating in a spatial and temporal expression (Simmons et al. 2008) combinatorial, but trophoblast-specific manner and and appear to target the maternal endometrium (Soares poorly understood processes linked to peculiarities in et al. 2007). the epigenetic landscape of trophoblast. There have The pregnancy-specific glycoproteins (PSGs) are also been a large number of gene family expansions secreted molecules that are abundantly produced by (Rawn & Cross 2008). These gene families may be primate and rodent placentas. They are related to the performing roles in processes such as maternal carcinoembryonic antigen cell adhesion molecules recognition of pregnancy, nutrient acquisition and (CEACAM) found on the surface of certain tumors and immune protection, thereby contributing to the unique selected normal somatic cells. There are 10 intact PSG functional needs of different placental forms. It is worth genes in the human genome and 17 in mouse (McLellan noting that ‘placenta-specific’ in this context means that et al. 2005), although it is almost impossible to assign such genes are disproportionately, but not necessarily orthologous members based on sequence identity. uniquely, expressed in the placenta. For example, it is Moreover, the organization of the domains in human not unusual for some placenta-specific gene products and mouse PSG proteins are quite different (McLellan to be elevated in cancer and germ cells. et al. 2005), raising the possibility that their roles in primates and humans may not be identical. PSGs are able to enter the maternal circulation and, in human, Placenta-specific gene families can accumulate to extraordinarily high concentrations Gene duplication provides a useful opportunity for in blood (200–400 µg/mL at term), but their roles natural selection to operate (Hughes 1994) and allows remain enigmatic. www.reproduction-online.org Reproduction (2016) 152 R179–R189

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access R186 R M Roberts and others

The interferon τ (IFNτ) proteins are products of the effectively silenced. As a result, the fate of most ERVs filamentous conceptus of ruminants and have been is gradual genetic degradation through mutation and mentioned earlier in the context of maternal recognition homologous recombination. Nevertheless, a minority of pregnancy. They have been described in no other of ERVs retain a whole or partially intact open reading taxa (Leaman & Roberts 1992). Within a species they frame potentially capable of producing a functional are well conserved, but considerable divergence protein (Weiss 2016). This point is particularly salient in is evident in inter-species comparisons. They are regard to the placenta, which in many species express a transcribed from multiple, structurally conserved range of ERVs that are involved in trophoblast function genes that have probably arisen by duplications and (Denner 2016). Of those ERVs expressed in the placenta, gene conversion events from another type 1 IFN gene, the most studied have originated from the envelope interferon omega (IFNW). Although builds of the (env) elements of the integrated viral DNA, and have bovine genome have suggested IFNτ to be a relatively been called syncytins (Lokossou et al. 2014). small gene family (Walker & Roberts 2009), a large In humans, ERVW1 (syncytin-1) facilitates the fusion of number of gene variants have been described in each mononucleated cytotrophoblasts to form multinucleated species and even within single conceptuses, suggesting STBs (Mi et al. 2000). This process involves the interaction that the families continue to diverge rapidly. The IFNT of ERVW1 with a ‘receptor’, most probably the neutral proteins are secreted from mononucleated trophoblasts amino acid transporter, SLC5A1, on a neighboring cell. and act on the uterus by binding to type I interferon The expression of ERVW1 is regulated by the placenta- receptors, with the period of release occurring before specific transcription factor GCM1 discussed earlier, via the trophoblast has formed definite attachment to the an enhancer element present in the long-terminal repeat uterine epithelium (Bazer et al. 1997, Roberts et al. (LTR) of the gene (Lin et al. 2005). It is also notable 1999). Another notable feature of the IFNτ is that these that ERVW1 is not involved in trophoblast fusion in proteins have retained typical features of other type I Old World monkeys, despite being present in their interferons, such as potent antiviral activity, although genomes (Cáceres et al. 2006). These animals make their primary role has shifted to a reproductive use of a distinct syncytin, ERVV2, for STB formation. function. Conceivably, the progenitor gene product in Conversely, ERVV2 is expressed in human placenta but the common ancestor of present-day ruminants served does not appear to be involved in cytotrophoblast fusion to protect the conceptus from viral infections. (Blaise et al. 2005). An important point illustrated here The pregnancy-associated glycoproteins (PAGs) is that expressed retroviral envelope genes (env) often are products of a gene family present in the placental fulfill similar roles across species, but few represent trophoblasts of swine and ruminants and most other orthologous genes. Instead, the majority has arisen as a even-toed ungulates (Wallace et al. 2015). They are result of independent integration events and coopted for related to aspartic proteinases, although some notably similar functions by different species. lack the capacity to cleave protein substrates due to A second env gene from a different endogenous modifications of normally conserved amino acids retrovirus (ERVFRD1; syncytin-2) is expressed in the around the active sites. The PAGs are particularly villous trophoblast of the human placenta (Blaise et al. complex in ruminants; in cattle, for example, there are 2003, Malassine et al. 2007) and is also believed to be approximately two dozen members along with some involved in trophoblast fusion events through interaction closely related paralogs. Most of the PAGs in ruminants with another transporter protein, MFSD2. ERVFRD1 has are expressed by specialized polyploid trophoblast been proposed to be immunosuppressive, an activity not cells (binucleate giant cells) discussed earlier. After shared by ERVW1 (Mangeney et al. 2007). Several other fusion, the contents of secretory granules within the ERV proteins, e.g. ERV3-1, and ERVK family members, binucleate cells are disgorged into the uterine stroma, including an antagonist of cell fusion (Sugimoto et al. and many of the released PAGs enter the maternal 2013) are expressed in the placenta, but the roles of most circulation and form the basis of useful pregnancy tests of them are even more obscure than that of ERVFRD1. for various ruminants, including dairy cows. The role In mouse placenta, the labyrinth layer, which is of PAGs is unknown, but their abundance suggests an the functional equivalent of human floating villous important function during pregnancy. trophoblast, forms the transport surface in contact with the maternal bloodstream. It is hemotrichorial, i.e. it has a cytotrophoblast layer overlaid by two STB Endogenous retroviruses and retroviral elements layers (Dupressoir et al. 2009). Two syncytin genes Ancestral retroviral infections have provided another (Syna & Synb), products of separate integration events, source of novel protein-coding genes that have played a are expressed in this tissue. The SYNB protein is role in placental evolution. To ensure that the viral genes primarily localized to the innermost STB layer, and, like do not replicate, the control elements of endogenous ERVFRD in the human, may have immunosuppressive retroviruses (ERVs) are usually highly methylated and activity, as well as roles in facilitating cell fusion

Reproduction (2016) 152 R179–R189 www.reproduction-online.org

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access The evolution of the placenta R187

(Mangeney et al. 2007). Neither of these gene products, Funding however, is related to human syncytins, except for the Support was received from Missouri Mission Enhancement fact they are derived from ERV genes and are expressed Funds (L C S), Food for the twenty-first century program at the placentally. University of Missouri (R M R & J A G), and a NIH Eunice Finally, endogenous retroviruses, with no obvious Kennedy Shriver National Institute of Child Health and Human homology to each other, have been described in the Development Grant (R01 HD069979) (R M R). placentas of a number of other species, including marsupials, ruminants, carnivores and lagomorphs (Denner 2016). In ruminants, they are mainly associated Acknowledgements with trophoblast binucleate cells that fuse with uterine The authors thank Dennis Reith for editorial help, and Susan epithelial cells, but are assumed in all these species to Roberts, Nico Zevallos and Dr Ye Yuan for assistance in play roles that are somewhat similar to syncytins in the preparing the figures. human placenta.

References Conclusions Ain R, Dai G, Dunmore JH, Godwin AR & Soares MJ 2004 A prolactin Placentas, whatever their anatomic features, share a family paralog regulates reproductive adaptations to a physiological number of common functions, all of which require stressor. PNAS 101 16543–16548. (doi:10.1073/pnas.0406185101) Amoroso E 1952 Placentation. In Marshall’s Physiology of Reproduction, cooperative interactions with the maternal system. pp 127–311. Ed A Parkes. Boston, MA, USA: Little Brown & Co. Placentas deal with nutrient and oxygen import, Bazer FW, Spencer TE & Ott TL 1997 Interferon tau: a novel pregnancy disposal of fetal waste products and gases, help to recognition signal. American Journal of Reproductive Immunology 37 physically retain the conceptus in the reproductive 412–420. (doi:10.1111/aji.1997.37.issue-6) Bazer FW, Spencer TE, Johnson GA, Burghardt RC & Wu G 2009 tract, commandeer the local maternal blood supply Comparative aspects of implantation. Reproduction 138 195–209. in some manner, release factors including metabolic (doi:10.1530/REP-09-0158) hormones to adjust the needs of the fetus to the Blackburn DG 2015 Evolution of vertebrate viviparity and specializations for fetal nutrition: a quantitative and qualitative analysis. Journal of resources provided by the mother, and provide Morphology 276 961–990. (doi:10.1002/jmor.v276.8) immune protection. Yet, despite these apparently Blackburn DG & Flemming AF 2012 Invasive implantation and intimate conserved functions placentas are arguably the least placental associations in a placentotrophic african lizard, Trachylepis conserved and the most rapidly evolving mammalian ivensi (scincidae). Journal of Morphology 273 137–159. (doi:10.1002/ jmor.11011) organs. These changes are speculated to be driven, at Blaise S, de Parseval N, Bénit L & Heidmann T 2003 Genomewide least in part by maternal–fetal conflict (Haig 1996). screening for fusogenic human endogenous retrovirus envelopes Placental divergence has, in turn, been promoted identifies syncytin 2, a gene conserved on primate evolution.PNAS 100 by selection for multiple kinds of genetic changes 13013–13018. (doi:10.1073/pnas.2132646100) Blaise S, de Parseval N & Heidmann T 2005 Functional characterization including (1) duplications and gene conversion of two newly identified human endogenous retrovirus coding envelope events to create large gene families that themselves genes. Retrovirology 2 1–4. (doi:10.1186/1742-4690-2-1) are continuing to diverge extensively; (2) co-opting of Burton GJ & Jauniaux E 2015 What is the placenta? American Journal of Obstetrics and Gynecology 213 S6 e1, S6–S8. (doi:10.1016/j. endogenous retrovirus-derived genes and gene control ajoq.2015.07.050) elements; (3) rapid evolution of placenta-specific Cáceres M, NCS Program & Thomas JW 2006 The gene of retroviral origin enhancers and promoter elements; and (4) imprinting. syncytin 1 is specific to hominoids and is inactive in old world monkeys. It is also possible that the hypomethylated state of Journal of Heredity 97 100–106. (doi:10.1093/jhered/esj011) Carcupino M, Baldacci A, Mazzini M & Franzoi P 2002 Functional the placental genome (Chuong 2013) has permitted significance of the male brood pouch in the reproductive strategies relaxed silencing of gene control elements, including of pipefishes and seahorses: a morphological and ultrastructural those of ERVs. Perhaps this feature of the placenta sets comparative study on three anatomically different pouches. Journal of Fish Biology 61 1465–1480. (doi:10.1111/jfb.2002.61.issue-6) the stage for increased opportunity for epistasis – the Carter AM 2016, posting date. Marsupial Frogs. [Online.] interactions of genes that are not allelic. For example, Chen Z, Hagen DE, Wang J, Elsik CG, Ji T, Siqueira LG, Hansen PJ & a harmful mutation in one gene may occasionally Rivera RM 2016 Global assessment of imprinted gene expression in become beneficial and confer increased fitness in the bovine conceptus by next generation sequencing. Epigenetics 11 501–516. (doi:10.1080/15592294.2016.1184805) the presence of a mutation in another gene (sign Chuong EB 2013 Retroviruses facilitate the rapid evolution of the mammalian epistasis) (Weinreich et al. 2005), possibly allowing placenta. BioEssays 35 853–861. (doi:10.1002/bies.201300059) both mutations to become fixed and the placenta to Cornelis G, Vernochet C, Malicorne S, Souquere S, Tzika AC, adapt to the constraints of a changing environment. Goodman SM, Catzeflis F, Robinson TJ, Milinkovitch MC, Pierron G et al. 2014 Retroviral envelope syncytin capture in an ancestrally diverged mammalian clade for placentation in the primitive Afrotherian tenrecs. PNAS 111 E4332–E4341. (doi:10.1073/pnas.1412268111) Declaration of interest Cross JC, Baczyk D, Dobric N, Hemberger M, Hughes M, Simmons DG, Yamamoto H & Kingdom JC 2003 Genes, development and evolution of The authors declare that there is no conflict of interest that the placenta. Placenta 24 123–130. (doi:10.1053/plac.2002.0887) could be perceived as prejudicing the impartiality of the Denner J 2016 Expression and function of endogenous retroviruses in the research reported. placenta. APMIS 124 31–43. (doi:10.1111/apm.12474) www.reproduction-online.org Reproduction (2016) 152 R179–R189

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access R188 R M Roberts and others

Dupressoir A, Vernochet C, Bawa O, Harper F, Pierron G, Opolon P & genetic disjunction between the fusogenic and immunosuppressive Heidmann T 2009 Syncytin-A knockout mice demonstrate the critical role activity of retroviral envelope proteins. PNAS 104 20534–20539. in placentation of a fusogenic, endogenous retrovirus-derived, envelope (doi:10.1073/pnas.0707873105) gene. PNAS 106 12127–12132. (doi:10.1073/pnas.0902925106) McLellan AS, Zimmermann W & Moore T 2005 Conservation of pregnancy- Enders AC & Carter AM 2004 What can comparative studies of placental specific glycoprotein (PSG) N domains following independent expansions structure tell us? – A review. Placenta 25 S3–S9. (doi:10.1016/j. of the gene families in rodents and primates. BMC Evolutionary Biology placenta.2004.01.020) 5 1–19. (doi:10.1186/1471-2148-5-1) Familari M, Au PC, de Iongh RU, Cruz Y & Selwood L 2016 Expression Mess A & Carter AM 2007 Evolution of the placenta during the early analysis of Cdx2 and Pou5f1 in a marsupial, the stripe-faced dunnart, radiation of placental mammals. Comparative Biochemistry and during early development. Molecular Reproduction and Development Physiology. Part A: Molecular & Integrative Physiology 148 769–779. 83 108–123. (doi:10.1002/mrd.22597) (doi:10.1016/j.cbpa.2007.01.029) Fowden AL & Constancia M 2012 Maternal-fetal resource allocation. Mi S, Lee X, Li X-P, Veldman GM, Finnerty H, Racie L, LaVallie E, Tang X-Y, Placenta 33 e1–e2. (doi:10.1016/j.placenta.2012.09.005) Edouard P, Howes S et al. 2000 Syncytin is a captive retroviral envelope Frankenberg S, Shaw G, Freyer C, Pask AJ & Renfree MB 2013 Early cell protein involved in human placental morphogenesis. Nature 403 lineage specification in a marsupial: a case for diverse mechanisms 785–789. (doi:10.1038/35001608) among mammals. Development 140 965–975. (doi:10.1242/dev.091629) Morrison JT, Bantilan NS, Wang VN, Nellett KM & Cruz YP 2013 Expression Freyer C, Zeller U & Renfree MB 2003 The marsupial placenta: a patterns of Oct4, Cdx2, Tead4, and Yap1 proteins during blastocyst phylogenetic analysis. Journal of Experimental Zoology Part A: formation in embryos of the marsupial, Monodelphis domestica Wagner. Comparative Experimental Biology 299A 59–77. (doi:10.1002/ Evolution & Development 15 171–185. (doi:10.1111/ede.v15.3) (ISSN)1097-010X) Murphy BF, Parker SL, Murphy CR & Thompson MB 2011 Placentation Friess AE, Sinowatz F, Skolek-Winnisch R & Traautner W 1980 The placenta in the eastern water skink (Eulamprus quoyii): a placentome-like of the pig. I. Finestructural changes of the placental barrier during structure in a lecithotrophic lizard. Journal of Anatomy 218 678–689. pregnancy. Anatomy and Embryology 158 179–191. (doi:10.1007/ (doi:10.1111/j.1469-7580.2011.01368.x) BF00315905) Painter DL & Moore MC 2005 Steroid hormone metabolism by the Friess AE, Sinowatz F, Skolek-Winnisch R & Trautner W 1981 The placenta chorioallantoic placenta of the mountain spiny lizard Sceloporus of the pig. II. The ultrastructure of the areolae. Anatomy and Embryology jarrovi as a possible mechanism for buffering maternal-fetal hormone 163 43–53. (doi:10.1007/BF00315769) exchange. Physiological and Biochemical Zoology 78 364–372. Haig D 1993 Genetic conflicts in human pregnancy. Quarterly Review of (doi:10.1086/430222) Biology 68 495–532. (doi:10.1086/418300) Pollux BJ, Meredith RW, Springer MS, Garland T & Reznick DN 2014 The Haig D 1996 Altercation of generations: genetic conflicts of pregnancy. evolution of the placenta drives a shift in sexual selection in livebearing American Journal of Reproductive Immunology 35 226–232. fish.Nature 513 233–236. (doi:10.1038/nature13451) (doi:10.1111/aji.1996.35.issue-3) Posfai E, Tam OH & Rossant J 2014 Mechanisms of pluripotency in vivo Haig D 2008 Placental growth hormone-related proteins and and in vitro. Current Topics in Developmental Biology 107 1–37. prolactin-related proteins. Placenta 29 S36–S41. (doi:10.1016/j. (doi:10.1016/B978-0-12-416022-4.00001-9) placenta.2007.09.010) Pyron RA & Burbrink FT 2014 Early origin of viviparity and multiple Hamlett WC, Eulitt AM, Jarrell RL & Kelly MA 1993 Uterogestation and reversions to oviparity in squamate reptiles. Ecology Letters 17 13–21. placentation in elasmobranchs. Journal of Experimental Zoology 266 (doi:10.1111/ele.2013.17.issue-1) 347–367. (doi:10.1002/(ISSN)1097-010X) Rawn SM & Cross JC 2008 The evolution, regulation, and function of Hemberger M 2013 Immune balance at the foeto-maternal interface as the placenta-specific genes.Annual Review of Cell and Developmental fulcrum of reproductive success. Journal of Reproductive Immunology Biology 24 159–181. (doi:10.1146/annurev.cellbio.24.110707.175418) 97 36–42. (doi:10.1016/j.jri.2012.10.006) Reik W, Constancia M, Fowden A, Anderson N, Dean W, Ferguson- Hubrecht AA 1904 The trophoblast: a rejoinder. Science 20 367–370. Smith A, Tycko B & Sibley C 2003 Regulation of supply and demand for (doi:10.1126/science.20.507.367) maternal nutrients in mammals by imprinted genes. Journal of Physiology Hughes AL 1994 The evolution of functionally novel proteins after gene 547 35–44. (doi:10.1113/jphysiol.2002.033274) duplication. Proceedings of the Royal Society B: Biological Sciences 256 Renegar RH, Bazer FW & Roberts RM 1982 Placental transport and 119–124. (doi:10.1098/rspb.1994.0058) distribution of uteroferrin in the fetal pig. Biology of Reproduction 27 Kalinka AT 2015 How did viviparity originate and evolve? Of conflict, 1247–1260. (doi:10.1095/biolreprod27.5.1247) co-option, and cryptic choice. BioEssays 37 721–731. (doi:10.1002/ Renfree MB 1982 Implantation and placentation. In Reproduction in bies.201400200) Mammals: Embryonic and Fetal Development, vol 2, pp 26–29. Eds Korsgaard B & Weber RE 1989 Maternal-Fetal Trophic and Respiraotry CR Austin & RV Short. Cambridge, UK: Cambridge University Press. Relationships. Berlin; New York: Springer-Verlag. Renfree MB 2010 Review: Marsupials: placental mammals with a Kwan L, Fris M, Rodd FH, Rowe L, Tuhela L & Panhuis TM 2015 An difference. Placenta 31 S21–S26. (doi:10.1016/j.placenta.2009.12.023) examination of the variation in maternal placentae across the genus Roberts RM, Ealy AD, Alexenko AP, Han CS & Ezashi T 1999 Trophoblast Poeciliopsis (Poeciliidae). Journal of Morphology 276 707–720. interferons. Placenta 20 259–264. (doi:10.1053/plac.1998.0381) (doi:10.1002/jmor.v276.6) Roberts RM, Xie S & Mathialagan N 1996 Maternal recognition of Leaman DW & Roberts RM 1992 Genes for the trophoblast interferons pregnancy. Biology of Reproduction 54 294–302. (doi:10.1095/ in sheep, goat, and musk ox and distribution of related genes among biolreprod54.2.294) mammals. Journal of Interferon Research 12 1–11. (doi:10.1089/ Savage JM 2002 The Amphibians and Reptiles of Costa Rica: A jir.1992.12.1) Herpetofauna Between Two Continents, Between Two Seas. Chicago, IL, Lin C, Lin M & Chen H 2005 Biochemical characterization of the human USA: University of Chicago Press. placental transcription factor GCMa/1. Biochemistry and Cell Biology 83 Selwood L & Johnson MH 2006 Trophoblast and hypoblast in the 188–195. (doi:10.1139/o05-026) monotreme, marsupial and eutherian mammal: evolution and origins. Lokossou A, Toudic C & Barbeau B 2014 Implication of human endogenous BioEssays 28 128–145. (doi:10.1002/(ISSN)1521-1878) retrovirus envelope proteins in placental functions. Viruses 6 4609. Simmons DG, Rawn S, Davies A, Hughes M & Cross JC 2008 Spatial and (doi:10.3390/v6114609) temporal expression of the 23 murine Prolactin/Placental Lactogen- Malassine A, Blaise S, Handschuh K, Lalucque H, Dupressoir A, related genes is not associated with their position in the locus. BMC Evain-Brion D & Heidmann T 2007 Expression of the fusogenic Genomics 9 352. (doi:10.1186/1471-2164-9-352) HERV-FRD Env glycoprotein (syncytin 2) in human placenta is restricted Soares MJ, Konno T & Alam SMK 2007 The prolactin family: effectors to villous cytotrophoblastic cells. Placenta 28 185–191. (doi:10.1016/j. of pregnancy-dependent adaptations. Trends in Endocrinology & placenta.2006.03.001) Metabolism 18 114–121. (doi:10.1016/j.tem.2007.02.005) Mangeney M, Renard M, Schlecht-Louf G, Bouallaga I, Heidmann O, Spencer TE, Johnson GA, Bazer FW, Burghardt RC & Palmarini M Letzelter C, Richaud A, Ducos B & Heidmann T 2007 Placental syncytins: 2007 Pregnancy recognition and conceptus implantation in domestic

Reproduction (2016) 152 R179–R189 www.reproduction-online.org

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access The evolution of the placenta R189

ruminants: roles of progesterone, interferons and endogenous Weinreich DM, Watson RA & Chao L 2005 Perspective: sign epistasis and retroviruses. Reproduction, Fertility, and Development 19 65–78. genetic constraint on evolutionary trajectories. Evolution 59 1165–1174. (doi:10.1071/RD06102) (doi:10.1111/j.0014-3820.2005.tb01768.x) Stewart JR 2015 Placental specializations in lecithotrophic viviparous Weiss RA 2016 Human endogenous retroviruses: friend or foe? APMIS 124 squamate reptiles. Journal of Experimental Zoology Part B: Molecular 4–10. (doi:10.1111/apm.12476) and Developmental Evolution 324 549–561. (doi:10.1002/jez.b.v324.6) Wildman DE, Chen C, Erez O, Grossman LI, Goodman M & Romero R Sugimoto J, Sugimoto M, Bernstein H, Jinno Y & Schust D 2013 A novel 2006 Evolution of the mammalian placenta revealed by phylogenetic human endogenous retroviral protein inhibits cell-cell fusion. Scientific analysis. PNAS 103 3203–3208. (doi:10.1073/pnas.0511344103) Reports 3 1462. (doi:10.1038/srep01462) Wilson AB, Vincent A, Ahnesjo I & Meyer A 2001 Male pregnancy in Thompson MB & Speake BK 2002 Energy and nutrient utilisation by seahorses and pipefishes (Family Syngnathidae): rapid diversification of embryonic reptiles. Comparative Biochemistry and Physiology Part A: paternal brood pouch morphology inferred from a molecular phylogeny. Molecular & Integrative Physiology 133 529–538. (doi:10.1016/S1095- Journal of Heredity 92 159–166. (doi:10.1093/jhered/92.2.159) 6433(02)00188-5) Wooding FB 1992 Current topic: the synepitheliochorial placenta of Van Dyke JU, Brandley MC & Thompson MB 2014 The evolution of ruminants: binucleate cell fusions and hormone production. Placenta 13 viviparity: molecular and genomic data from squamate reptiles advance 101–113. (doi:10.1016/0143-4004(92)90025-O) understanding of live birth in amniotes. Reproduction 147 R15–R26. Wourms JP & Lombardi J 1992 Reflections on the evolution of piscine (doi:10.1530/rep-13-0309) viviparity. American Zoologist 32 276–293. (doi:10.1093/icb/32.2.276) Wake MH 1993 Evolution of oviductal gestation in amphibians. Journal Zeller U & Freyer C 2001 Early ontogeny and placentation of the grey of Experimental Zoology 266 394–413. (doi:10.1002/(ISSN)1097-010X) short-tailed opossum, Monodelphis domestica (Didelphidae : Marsupialia): Walker AM & Roberts RM 2009 Characterization of the bovine type I contribution to the reconstruction of the marsupial morphotype. Journal IFN locus: rearrangements, expansions, and novel subfamilies. BMC of Zoological Systematics and Evolutionary Research 39 137–158. Genomics 10 1–15. (doi:10.1186/1471-2164-10-1) (doi:10.1046/j.1439-0469.2001.00167.x) Wallace RM, Pohler KG, Smith MF & Green JA 2015 Placental PAGs: gene origins, expression patterns, and use as markers of pregnancy. Reproduction 149 R115–R126. (doi:10.1530/rep-14-0485) Received 15 June 2016 Weekes HC 1935 A review ofplacentation among reptiles with particular First decision 11 July 2016 regard tofunction and evolution of the placenta. Proceedings of the Zoological Society of London 2 625–640. (doi:10.1111/j.1096-3642.1935. Revised manuscript received 13 July 2016 tb01686.x) Accepted 1 August 2016

www.reproduction-online.org Reproduction (2016) 152 R179–R189

Downloaded from Bioscientifica.com at 10/04/2021 01:13:48PM via free access