- Email: [email protected]
The evolving placenta: Convergent evolution of variations in the endotheliochorial relationship
Placenta 33 (2012) 319e326
Contents lists available at SciVerse ScienceDirect
Placenta journal homepage: www.elsevier.com/locate/placenta
Current topic
The evolving placenta: Convergent evolution of variations in the endotheliochorial relationship A.C. Enders a, *, A.M. Carter b a b
Department of Cell Biology and Human Anatomy, University of California Davis, School of Medicine, Davis CA 95616, USA Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 8 February 2012
Endotheliochorial placentas occur in orders from all four major clades of eutherian mammal. Species with this type of placenta include one of the smallest (pygmy shrew) and largest (African elephant) land mammals. The endotheliochorial placenta as a definitive form has an interhemal area consisting of maternal endothelium, interstitial lamina, trophoblast, individual or conjoint basal laminas, and fetal endothelium. We commonly think of such placentas as having hypertrophied maternal endothelium with abundant rough endoplasmic reticulum (rER), and as having hemophagous regions. Considering them as a whole, the trophoblast may be syncytial or cellular, fenestrated or nonfenestrated, and there may or may not be hemophagous regions. Variations also appear in the extent of hypertrophy of the maternal endothelium and in the abundance of rER in these cells. This combination of traits and a few other features produces many morphological variants. In addition to endotheliochorial as a definitive condition, a transitory endotheliochorial condition may appear in the course of forming a hemochorial placenta. In some emballonurid bats the early endotheliochorial placenta has two layers of trophoblast, but the definitive placenta lacks an outer syncytial trophoblast layer. In mollosid bats a well developed endotheliochorial placenta is present for a short time even after a definitive hemochorial placenta has developed in a different region. It is concluded that the endotheliochorial placenta is more widespread and diversified than originally thought, with the variant with cellular trophoblast in particular appearing in several species studied recently. Ó 2012 Published by Elsevier Ltd.
Keywords: Bats Carnivores Comparative placentation Endotheliochorial placentation Hemophagous regions Tenrecs Trophoblast
1. Introduction Endotheliochorial placentas occur in orders from all four major clades of eutherian mammal (Table 1). Species with this type of placenta include one of the smallest (pygmy shrew Suncus etruscus) and the largest (African elephant Loxodonta africana) land mammals. Endotheliochorial placentas have interhemal areas composed of maternal vessels with hypertrophied endothelium surrounded by an extracellular layer designated the interstitial lamina (Table 2). This is termed interstitial lamina since it is usually thicker and more complex than a typical basal lamina, and in addition it is interposed between epithelia of two different organisms rather than between an epithelium and surrounding stroma. Trophoblast with its basal lamina and fetal endothelium with or without a basal lamina are the remaining components of the interhemal area. The hypertrophy
* Corresponding author. Tel.:þ1 530 752 8719;fax:þ 1 530 752 8520. E-mail address: [email protected] (A.C. Enders). 0143-4004/$ e see front matter Ó 2012 Published by Elsevier Ltd. doi:10.1016/j.placenta.2012.02.008
of the maternal endothelium varies, however, and the trophoblast can be syncytial or cellular in a mono- or dichorial relationship. Additionally, there is variation in the location and complexity of the hemophagous regions, and many endotheliochorial placentas lack such regions entirely [1]. We here review current knowledge about this type of placentation. It is more widespread and diversified than originally thought, with the variant with cellular trophoblast appearing in several species studied recently. Moreover it is apparent, when surveying the variation across orders in the light of current concepts on mammalian evolution [2], that there has been convergent evolution both in the structure of the barrier and in accessory organs such as the hemophagous regions. 2. Variations in the interhemal barrier A well-characterized form of endotheliochorial placentation is found in the definitive placentas of mustelid carnivores including mink Neovison vison [3,4], ferret Mustela putorius furo [5,6], and sea otter Enhydra lutris [7]. As shown for the mink (Fig. 1A), there is
320
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
Table 1 Endotheliochorial placentation is widespread occurring in all four superordinal clades and ten different families of eutherian mammal. Families are listed for orders where more than one type of placentation is known to occur. Superordinal clade
Order
Representatives
Example
Euarchontoglires
Rodentia
Laurasiatheria
Scandentia Carnivora
Sciurid rodents (family) Kangaroo rats (family) Pocket mice (family) Spring hares (family) Tree shrews (order) Feliforms (suborder) a Caniforms (suborder)b Horseshoe bats (family) Mouse-tailed bats(family) Sheath-tailed bats (family) Slit-faced bats (family) Sucker-footed bats (family) Funnel-eared bats (family) Shrews (family) Moles (family) Sloths (suborder) Otter shrews (subfamily) Aardvark (order) Manatees (order) Elephants (order)
Tamias quadrivittatus Dipodomys merriami Perognathus parvus Pedetes capensis Tupaia glis Felis cattus Canis familiaris; Lobodon carcinophagus Rhinolophus rouxii Rhinopoma hardwickii Rhynchonycteris naso Nycteris thebaica Myzopoda aurita Natalus stramineus Blarina brevicauda Talpa europaea Bradypus tridactylus Micropotamogale lamottei Orycteropus afer Trichechus inunguis Loxodonta africana
Chiroptera
Soricomorpha Xenarthra Afrotheria
a b
Pilosa Afrosoricida Tubulidentata Sirenia Proboscidea
Hyenas (Family Hyaenidae) have endotheliochorial placentation. Includes pinnipeds.
a single layer of syncytial trophoblast, a thick interstitial lamina and a hypertrophied maternal endothelium. The maternal endothelial cells also have abundant undilated rough endoplasmic reticulum (rER). The extent of hypertrophy of these cells may be exaggerated or diminished by variations in the method of obtaining and fixing the placentas, especially by the difference between perfusion fixation at various pressures as opposed to immersion fixation of excised portions of the placenta. In this and most other endotheliochorial placentas there are places where trophoblast and maternal endothelial cells abut one another through the interstitial lamina. Although unrelated to the mustelids, the Nimba otter shrew Micropotamogale lamottei [8] and common tree shrew Tupaia glis [9] also show the general structure of a hypertrophied maternal endothelium, substantial interstitial lamina, and endotheliomonochorial placenta. An interesting variant on this pattern, typical of felid carnivores such as the domestic cat Felis catus (Fig. 1B), is the retention of numbers of decidual cells [10]. The dog Canis familiaris placenta, although similar to that of the cat, has only an occasional decidual cell in the labyrinth, which is less lamellar than that of the cat and has less hypertrophied maternal endothelial cells [11]. Table 2 Variations in interhemal regions found in mammals with endotheliochorial placentation. Trophoblast
Maternal endothelium
Examples
Syncytial trophoblast
Hypertrophied
Syncytial trophoblast with decidual cells Syncytial trophoblast fenestrated Syncytial trophoblast
Hypertrophied
Mustelid carnivores Otter shrews Tree shrews Felid carnivores
Cytotrophoblast and syncytial trophoblast (dichorial) Cellular trophoblast
Little hypertrophy
Cellular trophoblast
Non-hypertrophied
Hypertrophied Non-hypertrophied
Hypertrophied
Shrews Sloths Pinnipeds Springhaas Aardvark Moles
Some bats Manatees Heteromyid rodents Elephants
In shrews the syncytial trophoblast is elaborated with multiple folds and openings [12]. In places there is not only a direct pathway through the trophoblast, but in addition occasional processes from the maternal endothelial cells penetrate through the interstitial lamina and spaces in trophoblast to the basal lamina of the trophoblast (Fig. 2A, B). The maternal endothelium, although thick, has a limited amount of rER. The fetal endothelium is extraordinary in having extensive branched basal processes. Less well studied is the placenta of sloths [13]. As shown for the three-toed sloth Bradypus tridactylus [14], the syncytial trophoblast surrounding the maternal endothelium is relatively thick but has numerous openings towards the maternal endothelium and many spaces within the trophoblast, some of which contain a flocculent material (Fig. 2C, D). The internal spaces on the fetal side are smaller and, although some of them connect with thin channels toward the fetal endothelium, it has not been possible to trace direct pathways through the syncytial trophoblast. Consequently, although the trophoblast of the interhemal membrane is considered to be perforated, it is not identical to that of the shrews. Once again, however, a similar type of endotheliochorial placentation seems to have arisen by convergent evolution. There are a number of examples of endotheliochorial placentation with a single layer of syncytial trophoblast but with nonhypertrophied maternal endothelial cells. These are pinnipeds such as the seals (e.g. Lobodon carcinophagus) [15], the springhaas Pedetes capensis [16] and the aardvark Orycteropus afer [17]. These examples are taken from three of the four major clades of mammal (Table 1). Both the Egyptian slit-faced bat Nycteris thebaica [18] and the sucker-footed bat Myzopoda aurita [19] have a single layer of cellular trophoblast with hypertrophied maternal endothelium in the definitive placenta (Fig. 3). No endotheliodichorial stages have been seen in these species, but the very early stages of placental development have not been described. The Amazonian manatee Trichechus inunguis also has a cellular endotheliomonochorial placenta with moderately hypertrophied maternal endothelium [20]. The African elephant has a cellular endotheliomonochorial placenta but with little or no maternal endothelial hypertrophy [21]. In heteromyid rodents such as kangaroo rats Dipodomys merriami [22] and pocket mice Perognathus parvus, maternal
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
321
Fig. 1. A. American mink (Neovison vison). Hypertrophied maternal endothelium, thick interstitial lamina (il), and syncytial trophoblast (str) of irregular thickness separate maternal blood from the fetal vessel (fv). B. Domestic cat (Felis catus). A pale decidual cell (dc) is seen below the maternal vessel. A fetal vessel (fv) abuts the thick syncytial trophoblast, which is underlain by cellular trophoblast in this not-yet-mature placenta. Scale bar: 2.6 mm.
endothelium, trophoblast and fetal endothelium are extremely thin in places, and the interstitial lamina is also relatively thin; again the single layer of trophoblast is cellular (Fig. 4A). The European mole Talpa europaea has been described as having an endotheliodichorial placenta [23]. There is an inner cellular and outer syncytial layer of trophoblast and limited hypertrophy of the maternal endothelium. In the Mexican funnel-eared bat Natalus stramineus (Fig. 4B,C), the early placenta has a complete layer of cellular trophoblast underlying syncytial trophoblast that surrounds maternal vessels. The definitive placenta is endotheliomonochorial with a single layer of cellular trophoblast rather than syncytial trophoblast [24]. A similar situation is found in the whitelined bat Saccopteryx bilineata [24]. 3. Endotheliochorial as transition to hemochorial placentation It might be supposed that mammals with a definitive hemochorial placenta would retain the maternal endothelium at an earlier stage of development. Elsewhere we show that this transition seldom occurs [25]. In several bat families, however, the trophoblast dislodges the endothelial cells, although retaining a space for much of the basal lamina within the trophoblast [24]. The result is an intratrophoblastic lamina and space in a hemochorial placenta. A similar transition occurs in sciuromorph rodents such as the chipmunk Tamias quadrivittatus [24,25]. In mollosid bats a well-developed endotheliochorial placenta is present for a short time even after a definitive hemochorial placenta has developed in a different region [24].
4. Structure of the labyrinth All endotheliochorial placentas are considered to be labyrinthine, but this term covers a great deal of variation in structure. Some labyrinths maintain the irregularly coiled structure of the original maternal vessels, such as seen in the Nimba otter shrew Micropotamogale and white-lined bat Saccopteryx (Fig. 5A). In other species, during the process of extension of maternal vessels in the direction of the fetal surface of the placenta, the arrangement of the vessels becomes more parallel. In some instances, such as the cat [26] and Amazonian manatee [20], the maternal vessels lose much of their coiling and a parallel linear array similar to that often seen in hemochorial labyrinths is formed (Fig. 5B). In the mink, which has been studied extensively, it has been shown that the response to trophoblast is not only modification of endothelial cells and thickening of the basal lamina into an interstitial lamina, but also a series of changes in the shape, diameter, and interconnection of maternal vessels of the labyrinth. The diameter of the maternal vessels may increase between early and late placentas [27]. Since fetal capillaries run back from the maternal side, and maternal capillaries run down from the fetal side, the overall flow of the two vascular systems is countercurrent in most endotheliochorial placentas. However, it has been shown in the mink by using vascular casts that the relationship between fetal capillaries and maternal vessels within much of the labyrinth is more of a cross-current flow [28]. Vascular casts have also been useful in identifying hypertrophy of maternal endothelial cells by their intrusion into the lumen of the capillaries [27,28].
322
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
Fig. 2. A, B. Short-tailed shrew (Blarina brevicauda). In A, the syncytial trophoblast is a dark blue line between the thick endothelium of maternal vessels (mv) and the fetal vessels (fv). In B, the perforated nature of the syncytial trophoblast (str) with folds and spaces is seen underlying the thick maternal endothelium. Note the branched processes from fetal endothelial cells. A process from a maternal endothelial cell (*) extends through the area of the interstitial lamina (il) and abuts the basal lamina of the syncytial trophoblast. C, D. Three toed sloth (Bradypus tridactylus). In C, the endothelium of the maternal vessel (mv) is hypertrophied. The syncytial trophoblast (str) surrounding maternal vessels has light and dark areas. The light areas in C correspond to the spaces within syncytial trophoblast seen in D. The interstitial lamina (il) is thick but discontinuous. Fetal vessel (fv). Scale bar: 25 mm (A), 0.9 mm (B,D), 21 mm (C).
The interaction of trophoblast and endometrium results in an elongation of endometrial vessels in nearly all species. The maternal endothelial cells also show modification, as does the endothelial basal lamina, which is now situated between the base of the endothelium and the apical surface of the trophoblast. The morphology of the endometrium may also affect the definitive form of the placenta. In the majority of carnivores the first maternal vessels encountered by trophoblast are situated between endometrial glands. At this time there is both a syncytial trophoblast portion and an extensive underlying cellular trophoblast. Subsequently trophoblast extends into the mouths of the glands, accompanied by fetal mesenchyme, forming the first chorionic villi [10,27]. After destruction of the endometrial epithelium and underlying mesenchymal structures, the
remaining maternal vessels act as the center of the maternal vascular lobules [28], with lobulation more obvious in some animals such as the dog and less in some like the cat. In species with discoidal rather than zonary placentas, such as the Nimba otter shrew M. lamottei, trophoblast surrounds maternal vessels through much of the depth of the endometrium early in development [8]. Thus the gland structure does not appear to influence the final arrangement of the two sets of vessels, resulting in a more coiled than lamellar arrangement. Whereas there is relatively more thinning of the endometrium in the slow-developing cat placenta [29] than in the more rapidly developing mink placenta [27], the major increase in thickness of the labyrinth comes from elongation of the maternal vessels into the trophoblast. As Wooding et al. [30] have pointed out for these
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
323
Fig. 3. Egyptian slit-faced bat (Nycteris thebaica). Hypertrophied maternal endothelium is surrounded by a moderately thick interstitial lamina (il), underlain by cellular trophoblast, which is indented by fetal vessels. Scale bar: 1.9 mm.
two species and for the elephant, “growth of the lamellae or villi is the result of mutual maternofetal cell division and extension such that there is far more growth above the plane of implantation . than by invasion into the glands and endometrium by the trophoblast.” 5. Hemophagous regions The hemophagous regions facilitate fetal uptake of iron by phagocytosis of maternal red cells. This was first shown for the green border of the canine placenta by Lieberkühn [31]. In all hemophagous regions, the characteristic cell type is columnar trophoblast equipped with the cellular machinery for ingestion of red cells by endocytosis and their subsequent breakdown by lysosomes [32]. In the process of hemoglobin catabolism, heme oxygenase breaks the heme ring, releasing ferric iron and creating biliverdin. Biliverdin is converted to bilirubin and in the liver this is conjugated to glucuronic acid and excreted. In some placentas, however, the bilirubin is allowed to accumulate and form crystals of hematoidin [33]. There is considerable variation in the form and complexity of hemophagous regions. They can be single, as in the central hemophagous region of mustelid carnivores and emballonurid bats [34,35], or double, as in the African elephant and the green and brown borders of the domestic dog and domestic cat, respectively [29]. In addition pinnipeds, the aardvark and a few bats have marginal hemophagous regions [34]. Small multiple hemophagous regions can be found in some instances as in the sucker-footed bat Myzopoda (Fig. 6A). In the short-tailed shrew Blarina brevicauda, it is the trophoblast of the yolk sac placenta that phagocytoses maternal red cells (Fig. 6B), with iron pigments accumulating in the visceral yolk sac [36].
The blood can be released directly from the endometrium, as in the short-tailed shrew, dog and cat, or indirectly, from maternal vessels that are within the placenta, as in mustelid carnivores. Ordinarily blood release and ingestion begins after placental formation is underway and ceases well before parturition. Although these structures were originally called hematomas because of their often sack-like form, other authors suggested that this term was misleading and that emphasis should be placed on the erythrocyte uptake by designating the regions hemophagous organs rather than hematomas. We prefer hemophagous regions because they can be multiple and may be part of the endotheliochorial placenta per se [32]. A common and rather simple structure used for histotrophic nutrition is the areola [32]. It comprises columnar trophoblast cells in association with the mouth of a uterine gland. While the primary function of the trophoblast is to absorb uterine gland secretions, it is often heterophagous since it may take up tissue debris and red cells. Uptake of maternal red cells has been described in moles [23] and the manatee [20,37]. Many mammals have endotheliochorial placentation without hemophagous regions. They include species from five bat families [38], kangaroo rats [22] the springhaas [16], tree shrews and sloths [9,13]. In most of these species it is not known how the fetus acquires iron. In the Northern tree shrew Tupaia belangeri, there is evidence that the uterine glands secrete iron-rich histotrophe that is taken up by the yolk sac [39]. 6. Convergent evolution Phylogenetic relationships between mammals and their possible implications for the evolution of placentation have occupied scientists as far back as Huxley [40]. Recent analyses based on
324
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
Fig. 4. A. Great Plains pocket mouse (Perognathus parvus). Underlying the maternal vessel is a thin basal lamina rather than the thick interstitial lamina normally present in endotheliochorial placentas. The cellular trophoblast has areas of lipid and a thin flange (arrow) extending between the basal lamina of the maternal endothelium and its own basal lamina. The endothelium of the fetal vessel is also thin in this region. B, C. Mexican funnel-eared bat (Natalus stramineus). B. In the early placenta, the syncytial trophoblast around the maternal vessel is underlain by cellular trophoblast. Fetal vessel (fv). C. In the definitive placenta a single cellular trophoblast layer is present rather than a single syncytial trophoblast layer. Fetal vessels (fv). Scale bar: 1.2 mm (A), 3.7 mm (B,C).
molecular phylogenetics have been helpful in identifying four subordinal clades and have placed mammalian taxonomy on a sound footing [2,41]. Despite initial optimism that the revised mammalian tree might throw light on placental evolution [42], it is apparent that many character traits are distributed across orders in a manner that is best explained by convergent evolution. As an example, it cannot be known with certainty whether the ancestral placenta was endotheliochorial [43e45] or hemochorial [46,47] although probably it was invasive [48]. However Martin [45] has shown that either way there must have been multiple transformations between the two types. Indeed, the overriding impression from the present survey of endotheliochorial placentation is that convergent evolution has played a greater role than often recognized.
The variant with cellular trophoblast occurs in several species studied recently. Thus it is found in three of the four major clades of mammal, i.e. in bats (Laurasiatheria), kangaroo rats (Euarchontoglires) and manatees and elephants (Afrotheria). Whereas elephants and manatees share a common ancestor, there may have been convergent evolution of this placental variant in two families of bats, Nycteridae and Myzopodidae. Another example of convergent evolution is the highly fenestrated trophoblast found in shrews, which belong to Laurasiatheria, and sloths representing Xenarthra. Likewise hemophagous areas in various forms are scattered throughout the mammalian tree and found in all four major clades. An example is the marginal type found in several carnivores, which are assigned to Laurasiatheria, and in the aardvark and elephants from Afrotheria.
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
325
Fig. 5. A. White-lined bat (Saccopteryx bilineata). The coiled nature of the maternal vessels (mv) in this placenta is delineated by the cytokeratin-stained cellular trophoblast, which directly surrounds the maternal endothelium. B. Amazonian manatee (Trichechus inunguis). The linear nature of both fetal vessels (fv) and maternal vessels (mv) is shown in this section of the manatee placenta. Scale bar: 32 mm (A), 20 mm (B).
Not considered here is the variation in paraplacental regions (for example some are well vascularized, others are not). This feature and especially development of the yolk sac, also not considered here, add further diversity to placental formation in animals with endotheliochorial interhemal areas.
7. Topics requiring further study The widespread distribution of endotheliochorial placentas raises the question of what advantages this arrangement might provide. The presence of a maternal endothelial cell layer and interstitial lamina might be expected to limit the exchange of cells between fetal and maternal vascular systems. Does this postulated advantage overcome the disadvantage of lack of direct access of trophoblast to maternal blood for receptors, hormones, etc.? Neither the function of the rER in maternal endothelial cells nor the function of the contacts between trophoblast and maternal endothelium are known. Furthermore we do not know how animals with an endotheliochorial placenta but lacking a hemophagous region obtain sufficient iron transfer. Endotheliochorial placentas clearly need more investigation.
Acknowledgments We thank Thomas N. Blankenship, Steven M. Goodman, Carolyn Jones, Heinz Künzle, Vera da Silva, Peter J. Taylor and Peter Vogel for collaboration on several papers contributing to this study. We also acknowledge the following collections and their curators: Hubrecht Collection (Museum fur Naturkunde, Berlin) and Harland W. Mossman Collection (University of Wisconsin Zoological Museum).
References
Fig. 6. A. Sucker-footed bat (Myzopoda aurita). Trophoblast cells in hemophagous regions at the margins of the placental disk show erythrocyte ingestion. B. Short tailed shrew (Blarina brevicauda). Blood released into the uterine lumen is ingested by columnar trophoblast cells underlying the endoderm of the parietal yolk sac. Scale bar: 35 mm (A), 18 mm (B).
[1] Wooding FBP, Burton GJ. Comparative placentation. Berlin: Springer-Verlag; 2008. [2] Meredith RW, Janecka JE, Gatesy J, Ryder OA, Fisher CA, Telling EC, et al. Impacts of the cretaceous terrestrial revolution and KPg extinction on mammalian diversification. Science 2011;334:521e4. [3] Enders AC. Histological observations on the chorio-allantoic placenta of the mink. Anat Rec 1957;127:231e45. [4] Winther H, Leiser R, Pfarrer C, Dantzer V. Localization of micro- and intermediate filaments in non-pregnant uterus and placenta of the mink suggests involvement of maternal endothelial cells and periendothelial cells in blood flow regulation. Anat Embryol (Berl) 1999;200:253e63. [5] Strahl H, Ballmann E. Embryonalhüllen und Plazenta von Putorius furo. Berlin: Verl der Königl Akad der Wiss; 1915. [6] Lawn AM, Chiquoine AD. The ultrastructure of the placental labyrinth of the ferret (Mustela putorius furo). J Anat 1965;99:47e69. [7] Sinha AA, Mossman HW. Placentation of the sea otter. Am J Anat 1968;160: 795e805. [8] Carter AM, Blankenship TN, Enders AC, Vogel P. The fetal membranes of the otter shrews and a synapomorphy for Afrotheria. Placenta 2005;27:58e68. [9] Kaufmann P, Luckhardt M, Elger W. The structure of the tupaia placenta. II. Ultrastructure. Anat Embryol (Berl) 1985;171:211e21. [10] Leiser R, Koob B. Development and characteristics of placentation in a carnivore, the domestic cat. J Exp Zool 1993;266:642e56.
326
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
[11] Anderson JW. Ultrastructure of the placenta and fetal membranes of the dog. Anat Rec 1969;165:15e36. [12] Wimsatt WA, Enders AC, Mossman HW. A reexamination of the chorioallantoic placental membrane of a shrew, Blarina brevicauda: resolution of a controversy. Am J Anat 1973;138:207e33. [13] Wislocki GB. Observations on the gross and microscopic anatomy of the sloths (Bradypus griseus Gray and Choloepus hoffmani Peters). J Morph Physiol 1928; 46:317e97. [14] King BF, Pinheiro PB, Hunter RL. The fine structure of the placental labyrinth in the sloth, Bradypus tridactylus. Anat Rec 1982;202:15e22. [15] Sinha AA, Erickson AW. Ultrastructure of the placenta of Antarctic seals during the first third of pregnancy. Am J Anat 1974;141:263e7. [16] Owiti GEO, Oduor-Okelo D, Gombe S. Ultrastructure of the chorioallantoic placenta of the springhare (Pedetes capensis larvalis Hollister). Afr J Ecol 1985; 23:145e52. [17] Carter AM, Enders AC, Kunzle H, Oduor-Okelo D, Vogel P. Placentation in species of phylogenetic importance: the Afrotheria. Anim Reprod Sci 2004;8283:35e48. [18] Enders AC, Jones CJ, Taylor PJ, Carter AM. Placentation in the Egyptian slitfaced bat Nycteris thebaica (Chiroptera: Nycteridae). Placenta 2009;30:792e9. [19] Carter AM, Goodman SM, Enders AC. Female reproductive tract and placentation in sucker-footed bats (Chiroptera: Myzopodidae) endemic to Madagascar. Placenta 2008;29:484e91. [20] Carter AM, Miglino MA, Ambrosio CE, Santos TC, Rosas FC, Neto JA, et al. Placentation in the Amazonian manatee, Trichechus inunguis. Reprod Fert Dev 2008;20:537e45. [21] Wooding FB, Stewart F, Mathias S, Allen WR. Placentation in the African elephant, Loxodonta africanus: III. Ultrastructural and functional features of the placenta. Placenta 2005;26:449e70. [22] King BF, Tibbitts FD. The ultrastructure of the placental labyrinth in the kangaroo rat, Dipodomys. Anat Rec 1969;163:543e54. [23] Malassine A, Leiser R. Morphogenesis and fine structure of the near-term placenta of Talpa europaea: I. Endotheliochorial labyrinth. Placenta 1984;5: 145e58. [24] Enders AC, Blankenship TN, Lantz KC, Enders SS. Morphological variation in the interhemal areas of chorioallantoic placentae. Troph Res 1998;12:1e19. [25] Enders AC, Carter AM. The evolving placenta: different developmental paths to a hemochorial relationship. Placenta 2012;33(Suppl. A):S92e8. [26] Leiser R, Kohler T. The blood vessels of the cat girdle placenta. Observations on corrosion casts, scanning electron microscopical and histological studies. I. maternal vasculature. Anat Embryol (Berl) 1983;167:85e93. [27] Pfarrer C, Winther H, Leiser R, Dantzer V. The development of the endotheliochorial mink placenta: light microscopy and scanning electron microscopical morphometry of maternal vascular casts. Anat Embryol (Berl) 1999; 199:63e74. [28] Krebs C, Winther H, Dantzer V, Leiser R. Vascular interrelationships of nearterm mink placenta: light microscopy combined with scanning electron microscopy of corrosion casts. Microsc Res Tech 1997;38:125e36.
[29] Amoroso EC. Placentation. In: Parkes AS, editor. Marshall’s physiology of reproduction, vol. 2. London: Longmans Green and Co; 1952. p. 127e297. [30] Wooding FBP, Dantzer VB, Klisch K, Jones CJ, Forhead AJ. Glucose transporter 1 localisation throughout pregnancy in the carnivore placenta: light and electron microscope studies. Placenta 2007;28:453e64. [31] Lieberkühn N. Der grüne Saum der Hundeplacenta. Arch Anat Physiol 1889; 21:196e212. [32] Enders AC, Carter AM. Comparative placentation: some interesting modifications for histotrophic nutrition e a review. Placenta 2006;27(Suppl. A):11e6. [33] Carter AM, Blankenship TN, Künzle H, Enders AC. Development of the haemophagous region and labyrinth of the placenta of the tenrec, Echinops telfairi. Placenta 2005;26:251e61. [34] Burton GJ. Placental uptake of maternal erythrocytes: a comparative study. Placenta 1982;3:407e34. [35] Wimsatt WA, Gopalakrishna A. Occurrence of a placental hematoma in the primitive sheath-tailed bats (Emballonuridae), with observations on its structure, development and histochemistry. Am J Anat 1958;103:35e67. [36] King BF, Enders AC, Wimsatt WA. The annular hematoma of the shrew yolksac placenta. Am J Anat 1978;152:45e57. [37] Wislocki GB. The placentation of the manatee (Trichechus latorostris). Mem Museum Comp Zool Harv Coll 1935;54:158e78. [38] Carter AM, Mess A. Evolution of the placenta and associated reproductive characters in bats. J Exp Zoolog B Mol Dev Evol 2008;310:428e49. [39] Zeller U, Kuhn HJ. Postpartum erythrophagocytosis, iron storage and iron secretion in the endometrium of the tree shrew (Tupaia) during pregnancy. J Anat 1994;184:597e606. [40] Huxley TH. On the application of the laws of evolution to the arrangement of the Vertebrata, and more particularly of the Mammalia. Proc Zool Soc Lond 1880;43:649e62. [41] Murphy WJ, Eizirik E, Johnson WE, Zhang YP, Ryder OA, O’Brian SJ. Molecular phylogenetics and the origins of placental mammals. Nature 2001;409:614e8. [42] Carter AM. Evolution of the placenta and fetal membranes seen in the light of molecular phylogenetics. Placenta 2001;22:800e7. [43] Mess A, Carter AM. Evolutionary transformations of fetal membrane characters in Eutheria with special reference to Afrotheria. J Exp Zool (Mol Dev Evol) 2006;306B:140e63. [44] Mess A, Carter A. Review: evolution of the placenta during early radiation of placental mammals. Comp Biochem Physiol A Mol Integrat Physiol 2007;148: 769e79. [45] Martin RD. Evolution of placentation in Primates: implications of mammalian phylogeny. Evol Biol 2008;35:125e45. [46] Wildman DE, Chen C, Erez O, Grossman LI, Goodman M, Romero R. Evolution of the mammalian placenta revealed by phylogenetic analysis. Proc Natl Acad Sci USA 2006;103:3203e8. [47] Elliot MG, Crespi BJ. Phylogenetic evidence for early hemochorial placentation in Eutheria. Placenta 2009;30:923e1004. [48] Vogel P. The current molecular phylogeny of Eutherian mammals challenges previous interpretations of placental evolution. Placenta 2005;26:591e6.
Contents lists available at SciVerse ScienceDirect
Placenta journal homepage: www.elsevier.com/locate/placenta
Current topic
The evolving placenta: Convergent evolution of variations in the endotheliochorial relationship A.C. Enders a, *, A.M. Carter b a b
Department of Cell Biology and Human Anatomy, University of California Davis, School of Medicine, Davis CA 95616, USA Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 8 February 2012
Endotheliochorial placentas occur in orders from all four major clades of eutherian mammal. Species with this type of placenta include one of the smallest (pygmy shrew) and largest (African elephant) land mammals. The endotheliochorial placenta as a definitive form has an interhemal area consisting of maternal endothelium, interstitial lamina, trophoblast, individual or conjoint basal laminas, and fetal endothelium. We commonly think of such placentas as having hypertrophied maternal endothelium with abundant rough endoplasmic reticulum (rER), and as having hemophagous regions. Considering them as a whole, the trophoblast may be syncytial or cellular, fenestrated or nonfenestrated, and there may or may not be hemophagous regions. Variations also appear in the extent of hypertrophy of the maternal endothelium and in the abundance of rER in these cells. This combination of traits and a few other features produces many morphological variants. In addition to endotheliochorial as a definitive condition, a transitory endotheliochorial condition may appear in the course of forming a hemochorial placenta. In some emballonurid bats the early endotheliochorial placenta has two layers of trophoblast, but the definitive placenta lacks an outer syncytial trophoblast layer. In mollosid bats a well developed endotheliochorial placenta is present for a short time even after a definitive hemochorial placenta has developed in a different region. It is concluded that the endotheliochorial placenta is more widespread and diversified than originally thought, with the variant with cellular trophoblast in particular appearing in several species studied recently. Ó 2012 Published by Elsevier Ltd.
Keywords: Bats Carnivores Comparative placentation Endotheliochorial placentation Hemophagous regions Tenrecs Trophoblast
1. Introduction Endotheliochorial placentas occur in orders from all four major clades of eutherian mammal (Table 1). Species with this type of placenta include one of the smallest (pygmy shrew Suncus etruscus) and the largest (African elephant Loxodonta africana) land mammals. Endotheliochorial placentas have interhemal areas composed of maternal vessels with hypertrophied endothelium surrounded by an extracellular layer designated the interstitial lamina (Table 2). This is termed interstitial lamina since it is usually thicker and more complex than a typical basal lamina, and in addition it is interposed between epithelia of two different organisms rather than between an epithelium and surrounding stroma. Trophoblast with its basal lamina and fetal endothelium with or without a basal lamina are the remaining components of the interhemal area. The hypertrophy
* Corresponding author. Tel.:þ1 530 752 8719;fax:þ 1 530 752 8520. E-mail address: [email protected] (A.C. Enders). 0143-4004/$ e see front matter Ó 2012 Published by Elsevier Ltd. doi:10.1016/j.placenta.2012.02.008
of the maternal endothelium varies, however, and the trophoblast can be syncytial or cellular in a mono- or dichorial relationship. Additionally, there is variation in the location and complexity of the hemophagous regions, and many endotheliochorial placentas lack such regions entirely [1]. We here review current knowledge about this type of placentation. It is more widespread and diversified than originally thought, with the variant with cellular trophoblast appearing in several species studied recently. Moreover it is apparent, when surveying the variation across orders in the light of current concepts on mammalian evolution [2], that there has been convergent evolution both in the structure of the barrier and in accessory organs such as the hemophagous regions. 2. Variations in the interhemal barrier A well-characterized form of endotheliochorial placentation is found in the definitive placentas of mustelid carnivores including mink Neovison vison [3,4], ferret Mustela putorius furo [5,6], and sea otter Enhydra lutris [7]. As shown for the mink (Fig. 1A), there is
320
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
Table 1 Endotheliochorial placentation is widespread occurring in all four superordinal clades and ten different families of eutherian mammal. Families are listed for orders where more than one type of placentation is known to occur. Superordinal clade
Order
Representatives
Example
Euarchontoglires
Rodentia
Laurasiatheria
Scandentia Carnivora
Sciurid rodents (family) Kangaroo rats (family) Pocket mice (family) Spring hares (family) Tree shrews (order) Feliforms (suborder) a Caniforms (suborder)b Horseshoe bats (family) Mouse-tailed bats(family) Sheath-tailed bats (family) Slit-faced bats (family) Sucker-footed bats (family) Funnel-eared bats (family) Shrews (family) Moles (family) Sloths (suborder) Otter shrews (subfamily) Aardvark (order) Manatees (order) Elephants (order)
Tamias quadrivittatus Dipodomys merriami Perognathus parvus Pedetes capensis Tupaia glis Felis cattus Canis familiaris; Lobodon carcinophagus Rhinolophus rouxii Rhinopoma hardwickii Rhynchonycteris naso Nycteris thebaica Myzopoda aurita Natalus stramineus Blarina brevicauda Talpa europaea Bradypus tridactylus Micropotamogale lamottei Orycteropus afer Trichechus inunguis Loxodonta africana
Chiroptera
Soricomorpha Xenarthra Afrotheria
a b
Pilosa Afrosoricida Tubulidentata Sirenia Proboscidea
Hyenas (Family Hyaenidae) have endotheliochorial placentation. Includes pinnipeds.
a single layer of syncytial trophoblast, a thick interstitial lamina and a hypertrophied maternal endothelium. The maternal endothelial cells also have abundant undilated rough endoplasmic reticulum (rER). The extent of hypertrophy of these cells may be exaggerated or diminished by variations in the method of obtaining and fixing the placentas, especially by the difference between perfusion fixation at various pressures as opposed to immersion fixation of excised portions of the placenta. In this and most other endotheliochorial placentas there are places where trophoblast and maternal endothelial cells abut one another through the interstitial lamina. Although unrelated to the mustelids, the Nimba otter shrew Micropotamogale lamottei [8] and common tree shrew Tupaia glis [9] also show the general structure of a hypertrophied maternal endothelium, substantial interstitial lamina, and endotheliomonochorial placenta. An interesting variant on this pattern, typical of felid carnivores such as the domestic cat Felis catus (Fig. 1B), is the retention of numbers of decidual cells [10]. The dog Canis familiaris placenta, although similar to that of the cat, has only an occasional decidual cell in the labyrinth, which is less lamellar than that of the cat and has less hypertrophied maternal endothelial cells [11]. Table 2 Variations in interhemal regions found in mammals with endotheliochorial placentation. Trophoblast
Maternal endothelium
Examples
Syncytial trophoblast
Hypertrophied
Syncytial trophoblast with decidual cells Syncytial trophoblast fenestrated Syncytial trophoblast
Hypertrophied
Mustelid carnivores Otter shrews Tree shrews Felid carnivores
Cytotrophoblast and syncytial trophoblast (dichorial) Cellular trophoblast
Little hypertrophy
Cellular trophoblast
Non-hypertrophied
Hypertrophied Non-hypertrophied
Hypertrophied
Shrews Sloths Pinnipeds Springhaas Aardvark Moles
Some bats Manatees Heteromyid rodents Elephants
In shrews the syncytial trophoblast is elaborated with multiple folds and openings [12]. In places there is not only a direct pathway through the trophoblast, but in addition occasional processes from the maternal endothelial cells penetrate through the interstitial lamina and spaces in trophoblast to the basal lamina of the trophoblast (Fig. 2A, B). The maternal endothelium, although thick, has a limited amount of rER. The fetal endothelium is extraordinary in having extensive branched basal processes. Less well studied is the placenta of sloths [13]. As shown for the three-toed sloth Bradypus tridactylus [14], the syncytial trophoblast surrounding the maternal endothelium is relatively thick but has numerous openings towards the maternal endothelium and many spaces within the trophoblast, some of which contain a flocculent material (Fig. 2C, D). The internal spaces on the fetal side are smaller and, although some of them connect with thin channels toward the fetal endothelium, it has not been possible to trace direct pathways through the syncytial trophoblast. Consequently, although the trophoblast of the interhemal membrane is considered to be perforated, it is not identical to that of the shrews. Once again, however, a similar type of endotheliochorial placentation seems to have arisen by convergent evolution. There are a number of examples of endotheliochorial placentation with a single layer of syncytial trophoblast but with nonhypertrophied maternal endothelial cells. These are pinnipeds such as the seals (e.g. Lobodon carcinophagus) [15], the springhaas Pedetes capensis [16] and the aardvark Orycteropus afer [17]. These examples are taken from three of the four major clades of mammal (Table 1). Both the Egyptian slit-faced bat Nycteris thebaica [18] and the sucker-footed bat Myzopoda aurita [19] have a single layer of cellular trophoblast with hypertrophied maternal endothelium in the definitive placenta (Fig. 3). No endotheliodichorial stages have been seen in these species, but the very early stages of placental development have not been described. The Amazonian manatee Trichechus inunguis also has a cellular endotheliomonochorial placenta with moderately hypertrophied maternal endothelium [20]. The African elephant has a cellular endotheliomonochorial placenta but with little or no maternal endothelial hypertrophy [21]. In heteromyid rodents such as kangaroo rats Dipodomys merriami [22] and pocket mice Perognathus parvus, maternal
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
321
Fig. 1. A. American mink (Neovison vison). Hypertrophied maternal endothelium, thick interstitial lamina (il), and syncytial trophoblast (str) of irregular thickness separate maternal blood from the fetal vessel (fv). B. Domestic cat (Felis catus). A pale decidual cell (dc) is seen below the maternal vessel. A fetal vessel (fv) abuts the thick syncytial trophoblast, which is underlain by cellular trophoblast in this not-yet-mature placenta. Scale bar: 2.6 mm.
endothelium, trophoblast and fetal endothelium are extremely thin in places, and the interstitial lamina is also relatively thin; again the single layer of trophoblast is cellular (Fig. 4A). The European mole Talpa europaea has been described as having an endotheliodichorial placenta [23]. There is an inner cellular and outer syncytial layer of trophoblast and limited hypertrophy of the maternal endothelium. In the Mexican funnel-eared bat Natalus stramineus (Fig. 4B,C), the early placenta has a complete layer of cellular trophoblast underlying syncytial trophoblast that surrounds maternal vessels. The definitive placenta is endotheliomonochorial with a single layer of cellular trophoblast rather than syncytial trophoblast [24]. A similar situation is found in the whitelined bat Saccopteryx bilineata [24]. 3. Endotheliochorial as transition to hemochorial placentation It might be supposed that mammals with a definitive hemochorial placenta would retain the maternal endothelium at an earlier stage of development. Elsewhere we show that this transition seldom occurs [25]. In several bat families, however, the trophoblast dislodges the endothelial cells, although retaining a space for much of the basal lamina within the trophoblast [24]. The result is an intratrophoblastic lamina and space in a hemochorial placenta. A similar transition occurs in sciuromorph rodents such as the chipmunk Tamias quadrivittatus [24,25]. In mollosid bats a well-developed endotheliochorial placenta is present for a short time even after a definitive hemochorial placenta has developed in a different region [24].
4. Structure of the labyrinth All endotheliochorial placentas are considered to be labyrinthine, but this term covers a great deal of variation in structure. Some labyrinths maintain the irregularly coiled structure of the original maternal vessels, such as seen in the Nimba otter shrew Micropotamogale and white-lined bat Saccopteryx (Fig. 5A). In other species, during the process of extension of maternal vessels in the direction of the fetal surface of the placenta, the arrangement of the vessels becomes more parallel. In some instances, such as the cat [26] and Amazonian manatee [20], the maternal vessels lose much of their coiling and a parallel linear array similar to that often seen in hemochorial labyrinths is formed (Fig. 5B). In the mink, which has been studied extensively, it has been shown that the response to trophoblast is not only modification of endothelial cells and thickening of the basal lamina into an interstitial lamina, but also a series of changes in the shape, diameter, and interconnection of maternal vessels of the labyrinth. The diameter of the maternal vessels may increase between early and late placentas [27]. Since fetal capillaries run back from the maternal side, and maternal capillaries run down from the fetal side, the overall flow of the two vascular systems is countercurrent in most endotheliochorial placentas. However, it has been shown in the mink by using vascular casts that the relationship between fetal capillaries and maternal vessels within much of the labyrinth is more of a cross-current flow [28]. Vascular casts have also been useful in identifying hypertrophy of maternal endothelial cells by their intrusion into the lumen of the capillaries [27,28].
322
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
Fig. 2. A, B. Short-tailed shrew (Blarina brevicauda). In A, the syncytial trophoblast is a dark blue line between the thick endothelium of maternal vessels (mv) and the fetal vessels (fv). In B, the perforated nature of the syncytial trophoblast (str) with folds and spaces is seen underlying the thick maternal endothelium. Note the branched processes from fetal endothelial cells. A process from a maternal endothelial cell (*) extends through the area of the interstitial lamina (il) and abuts the basal lamina of the syncytial trophoblast. C, D. Three toed sloth (Bradypus tridactylus). In C, the endothelium of the maternal vessel (mv) is hypertrophied. The syncytial trophoblast (str) surrounding maternal vessels has light and dark areas. The light areas in C correspond to the spaces within syncytial trophoblast seen in D. The interstitial lamina (il) is thick but discontinuous. Fetal vessel (fv). Scale bar: 25 mm (A), 0.9 mm (B,D), 21 mm (C).
The interaction of trophoblast and endometrium results in an elongation of endometrial vessels in nearly all species. The maternal endothelial cells also show modification, as does the endothelial basal lamina, which is now situated between the base of the endothelium and the apical surface of the trophoblast. The morphology of the endometrium may also affect the definitive form of the placenta. In the majority of carnivores the first maternal vessels encountered by trophoblast are situated between endometrial glands. At this time there is both a syncytial trophoblast portion and an extensive underlying cellular trophoblast. Subsequently trophoblast extends into the mouths of the glands, accompanied by fetal mesenchyme, forming the first chorionic villi [10,27]. After destruction of the endometrial epithelium and underlying mesenchymal structures, the
remaining maternal vessels act as the center of the maternal vascular lobules [28], with lobulation more obvious in some animals such as the dog and less in some like the cat. In species with discoidal rather than zonary placentas, such as the Nimba otter shrew M. lamottei, trophoblast surrounds maternal vessels through much of the depth of the endometrium early in development [8]. Thus the gland structure does not appear to influence the final arrangement of the two sets of vessels, resulting in a more coiled than lamellar arrangement. Whereas there is relatively more thinning of the endometrium in the slow-developing cat placenta [29] than in the more rapidly developing mink placenta [27], the major increase in thickness of the labyrinth comes from elongation of the maternal vessels into the trophoblast. As Wooding et al. [30] have pointed out for these
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
323
Fig. 3. Egyptian slit-faced bat (Nycteris thebaica). Hypertrophied maternal endothelium is surrounded by a moderately thick interstitial lamina (il), underlain by cellular trophoblast, which is indented by fetal vessels. Scale bar: 1.9 mm.
two species and for the elephant, “growth of the lamellae or villi is the result of mutual maternofetal cell division and extension such that there is far more growth above the plane of implantation . than by invasion into the glands and endometrium by the trophoblast.” 5. Hemophagous regions The hemophagous regions facilitate fetal uptake of iron by phagocytosis of maternal red cells. This was first shown for the green border of the canine placenta by Lieberkühn [31]. In all hemophagous regions, the characteristic cell type is columnar trophoblast equipped with the cellular machinery for ingestion of red cells by endocytosis and their subsequent breakdown by lysosomes [32]. In the process of hemoglobin catabolism, heme oxygenase breaks the heme ring, releasing ferric iron and creating biliverdin. Biliverdin is converted to bilirubin and in the liver this is conjugated to glucuronic acid and excreted. In some placentas, however, the bilirubin is allowed to accumulate and form crystals of hematoidin [33]. There is considerable variation in the form and complexity of hemophagous regions. They can be single, as in the central hemophagous region of mustelid carnivores and emballonurid bats [34,35], or double, as in the African elephant and the green and brown borders of the domestic dog and domestic cat, respectively [29]. In addition pinnipeds, the aardvark and a few bats have marginal hemophagous regions [34]. Small multiple hemophagous regions can be found in some instances as in the sucker-footed bat Myzopoda (Fig. 6A). In the short-tailed shrew Blarina brevicauda, it is the trophoblast of the yolk sac placenta that phagocytoses maternal red cells (Fig. 6B), with iron pigments accumulating in the visceral yolk sac [36].
The blood can be released directly from the endometrium, as in the short-tailed shrew, dog and cat, or indirectly, from maternal vessels that are within the placenta, as in mustelid carnivores. Ordinarily blood release and ingestion begins after placental formation is underway and ceases well before parturition. Although these structures were originally called hematomas because of their often sack-like form, other authors suggested that this term was misleading and that emphasis should be placed on the erythrocyte uptake by designating the regions hemophagous organs rather than hematomas. We prefer hemophagous regions because they can be multiple and may be part of the endotheliochorial placenta per se [32]. A common and rather simple structure used for histotrophic nutrition is the areola [32]. It comprises columnar trophoblast cells in association with the mouth of a uterine gland. While the primary function of the trophoblast is to absorb uterine gland secretions, it is often heterophagous since it may take up tissue debris and red cells. Uptake of maternal red cells has been described in moles [23] and the manatee [20,37]. Many mammals have endotheliochorial placentation without hemophagous regions. They include species from five bat families [38], kangaroo rats [22] the springhaas [16], tree shrews and sloths [9,13]. In most of these species it is not known how the fetus acquires iron. In the Northern tree shrew Tupaia belangeri, there is evidence that the uterine glands secrete iron-rich histotrophe that is taken up by the yolk sac [39]. 6. Convergent evolution Phylogenetic relationships between mammals and their possible implications for the evolution of placentation have occupied scientists as far back as Huxley [40]. Recent analyses based on
324
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
Fig. 4. A. Great Plains pocket mouse (Perognathus parvus). Underlying the maternal vessel is a thin basal lamina rather than the thick interstitial lamina normally present in endotheliochorial placentas. The cellular trophoblast has areas of lipid and a thin flange (arrow) extending between the basal lamina of the maternal endothelium and its own basal lamina. The endothelium of the fetal vessel is also thin in this region. B, C. Mexican funnel-eared bat (Natalus stramineus). B. In the early placenta, the syncytial trophoblast around the maternal vessel is underlain by cellular trophoblast. Fetal vessel (fv). C. In the definitive placenta a single cellular trophoblast layer is present rather than a single syncytial trophoblast layer. Fetal vessels (fv). Scale bar: 1.2 mm (A), 3.7 mm (B,C).
molecular phylogenetics have been helpful in identifying four subordinal clades and have placed mammalian taxonomy on a sound footing [2,41]. Despite initial optimism that the revised mammalian tree might throw light on placental evolution [42], it is apparent that many character traits are distributed across orders in a manner that is best explained by convergent evolution. As an example, it cannot be known with certainty whether the ancestral placenta was endotheliochorial [43e45] or hemochorial [46,47] although probably it was invasive [48]. However Martin [45] has shown that either way there must have been multiple transformations between the two types. Indeed, the overriding impression from the present survey of endotheliochorial placentation is that convergent evolution has played a greater role than often recognized.
The variant with cellular trophoblast occurs in several species studied recently. Thus it is found in three of the four major clades of mammal, i.e. in bats (Laurasiatheria), kangaroo rats (Euarchontoglires) and manatees and elephants (Afrotheria). Whereas elephants and manatees share a common ancestor, there may have been convergent evolution of this placental variant in two families of bats, Nycteridae and Myzopodidae. Another example of convergent evolution is the highly fenestrated trophoblast found in shrews, which belong to Laurasiatheria, and sloths representing Xenarthra. Likewise hemophagous areas in various forms are scattered throughout the mammalian tree and found in all four major clades. An example is the marginal type found in several carnivores, which are assigned to Laurasiatheria, and in the aardvark and elephants from Afrotheria.
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
325
Fig. 5. A. White-lined bat (Saccopteryx bilineata). The coiled nature of the maternal vessels (mv) in this placenta is delineated by the cytokeratin-stained cellular trophoblast, which directly surrounds the maternal endothelium. B. Amazonian manatee (Trichechus inunguis). The linear nature of both fetal vessels (fv) and maternal vessels (mv) is shown in this section of the manatee placenta. Scale bar: 32 mm (A), 20 mm (B).
Not considered here is the variation in paraplacental regions (for example some are well vascularized, others are not). This feature and especially development of the yolk sac, also not considered here, add further diversity to placental formation in animals with endotheliochorial interhemal areas.
7. Topics requiring further study The widespread distribution of endotheliochorial placentas raises the question of what advantages this arrangement might provide. The presence of a maternal endothelial cell layer and interstitial lamina might be expected to limit the exchange of cells between fetal and maternal vascular systems. Does this postulated advantage overcome the disadvantage of lack of direct access of trophoblast to maternal blood for receptors, hormones, etc.? Neither the function of the rER in maternal endothelial cells nor the function of the contacts between trophoblast and maternal endothelium are known. Furthermore we do not know how animals with an endotheliochorial placenta but lacking a hemophagous region obtain sufficient iron transfer. Endotheliochorial placentas clearly need more investigation.
Acknowledgments We thank Thomas N. Blankenship, Steven M. Goodman, Carolyn Jones, Heinz Künzle, Vera da Silva, Peter J. Taylor and Peter Vogel for collaboration on several papers contributing to this study. We also acknowledge the following collections and their curators: Hubrecht Collection (Museum fur Naturkunde, Berlin) and Harland W. Mossman Collection (University of Wisconsin Zoological Museum).
References
Fig. 6. A. Sucker-footed bat (Myzopoda aurita). Trophoblast cells in hemophagous regions at the margins of the placental disk show erythrocyte ingestion. B. Short tailed shrew (Blarina brevicauda). Blood released into the uterine lumen is ingested by columnar trophoblast cells underlying the endoderm of the parietal yolk sac. Scale bar: 35 mm (A), 18 mm (B).
[1] Wooding FBP, Burton GJ. Comparative placentation. Berlin: Springer-Verlag; 2008. [2] Meredith RW, Janecka JE, Gatesy J, Ryder OA, Fisher CA, Telling EC, et al. Impacts of the cretaceous terrestrial revolution and KPg extinction on mammalian diversification. Science 2011;334:521e4. [3] Enders AC. Histological observations on the chorio-allantoic placenta of the mink. Anat Rec 1957;127:231e45. [4] Winther H, Leiser R, Pfarrer C, Dantzer V. Localization of micro- and intermediate filaments in non-pregnant uterus and placenta of the mink suggests involvement of maternal endothelial cells and periendothelial cells in blood flow regulation. Anat Embryol (Berl) 1999;200:253e63. [5] Strahl H, Ballmann E. Embryonalhüllen und Plazenta von Putorius furo. Berlin: Verl der Königl Akad der Wiss; 1915. [6] Lawn AM, Chiquoine AD. The ultrastructure of the placental labyrinth of the ferret (Mustela putorius furo). J Anat 1965;99:47e69. [7] Sinha AA, Mossman HW. Placentation of the sea otter. Am J Anat 1968;160: 795e805. [8] Carter AM, Blankenship TN, Enders AC, Vogel P. The fetal membranes of the otter shrews and a synapomorphy for Afrotheria. Placenta 2005;27:58e68. [9] Kaufmann P, Luckhardt M, Elger W. The structure of the tupaia placenta. II. Ultrastructure. Anat Embryol (Berl) 1985;171:211e21. [10] Leiser R, Koob B. Development and characteristics of placentation in a carnivore, the domestic cat. J Exp Zool 1993;266:642e56.
326
A.C. Enders, A.M. Carter / Placenta 33 (2012) 319e326
[11] Anderson JW. Ultrastructure of the placenta and fetal membranes of the dog. Anat Rec 1969;165:15e36. [12] Wimsatt WA, Enders AC, Mossman HW. A reexamination of the chorioallantoic placental membrane of a shrew, Blarina brevicauda: resolution of a controversy. Am J Anat 1973;138:207e33. [13] Wislocki GB. Observations on the gross and microscopic anatomy of the sloths (Bradypus griseus Gray and Choloepus hoffmani Peters). J Morph Physiol 1928; 46:317e97. [14] King BF, Pinheiro PB, Hunter RL. The fine structure of the placental labyrinth in the sloth, Bradypus tridactylus. Anat Rec 1982;202:15e22. [15] Sinha AA, Erickson AW. Ultrastructure of the placenta of Antarctic seals during the first third of pregnancy. Am J Anat 1974;141:263e7. [16] Owiti GEO, Oduor-Okelo D, Gombe S. Ultrastructure of the chorioallantoic placenta of the springhare (Pedetes capensis larvalis Hollister). Afr J Ecol 1985; 23:145e52. [17] Carter AM, Enders AC, Kunzle H, Oduor-Okelo D, Vogel P. Placentation in species of phylogenetic importance: the Afrotheria. Anim Reprod Sci 2004;8283:35e48. [18] Enders AC, Jones CJ, Taylor PJ, Carter AM. Placentation in the Egyptian slitfaced bat Nycteris thebaica (Chiroptera: Nycteridae). Placenta 2009;30:792e9. [19] Carter AM, Goodman SM, Enders AC. Female reproductive tract and placentation in sucker-footed bats (Chiroptera: Myzopodidae) endemic to Madagascar. Placenta 2008;29:484e91. [20] Carter AM, Miglino MA, Ambrosio CE, Santos TC, Rosas FC, Neto JA, et al. Placentation in the Amazonian manatee, Trichechus inunguis. Reprod Fert Dev 2008;20:537e45. [21] Wooding FB, Stewart F, Mathias S, Allen WR. Placentation in the African elephant, Loxodonta africanus: III. Ultrastructural and functional features of the placenta. Placenta 2005;26:449e70. [22] King BF, Tibbitts FD. The ultrastructure of the placental labyrinth in the kangaroo rat, Dipodomys. Anat Rec 1969;163:543e54. [23] Malassine A, Leiser R. Morphogenesis and fine structure of the near-term placenta of Talpa europaea: I. Endotheliochorial labyrinth. Placenta 1984;5: 145e58. [24] Enders AC, Blankenship TN, Lantz KC, Enders SS. Morphological variation in the interhemal areas of chorioallantoic placentae. Troph Res 1998;12:1e19. [25] Enders AC, Carter AM. The evolving placenta: different developmental paths to a hemochorial relationship. Placenta 2012;33(Suppl. A):S92e8. [26] Leiser R, Kohler T. The blood vessels of the cat girdle placenta. Observations on corrosion casts, scanning electron microscopical and histological studies. I. maternal vasculature. Anat Embryol (Berl) 1983;167:85e93. [27] Pfarrer C, Winther H, Leiser R, Dantzer V. The development of the endotheliochorial mink placenta: light microscopy and scanning electron microscopical morphometry of maternal vascular casts. Anat Embryol (Berl) 1999; 199:63e74. [28] Krebs C, Winther H, Dantzer V, Leiser R. Vascular interrelationships of nearterm mink placenta: light microscopy combined with scanning electron microscopy of corrosion casts. Microsc Res Tech 1997;38:125e36.
[29] Amoroso EC. Placentation. In: Parkes AS, editor. Marshall’s physiology of reproduction, vol. 2. London: Longmans Green and Co; 1952. p. 127e297. [30] Wooding FBP, Dantzer VB, Klisch K, Jones CJ, Forhead AJ. Glucose transporter 1 localisation throughout pregnancy in the carnivore placenta: light and electron microscope studies. Placenta 2007;28:453e64. [31] Lieberkühn N. Der grüne Saum der Hundeplacenta. Arch Anat Physiol 1889; 21:196e212. [32] Enders AC, Carter AM. Comparative placentation: some interesting modifications for histotrophic nutrition e a review. Placenta 2006;27(Suppl. A):11e6. [33] Carter AM, Blankenship TN, Künzle H, Enders AC. Development of the haemophagous region and labyrinth of the placenta of the tenrec, Echinops telfairi. Placenta 2005;26:251e61. [34] Burton GJ. Placental uptake of maternal erythrocytes: a comparative study. Placenta 1982;3:407e34. [35] Wimsatt WA, Gopalakrishna A. Occurrence of a placental hematoma in the primitive sheath-tailed bats (Emballonuridae), with observations on its structure, development and histochemistry. Am J Anat 1958;103:35e67. [36] King BF, Enders AC, Wimsatt WA. The annular hematoma of the shrew yolksac placenta. Am J Anat 1978;152:45e57. [37] Wislocki GB. The placentation of the manatee (Trichechus latorostris). Mem Museum Comp Zool Harv Coll 1935;54:158e78. [38] Carter AM, Mess A. Evolution of the placenta and associated reproductive characters in bats. J Exp Zoolog B Mol Dev Evol 2008;310:428e49. [39] Zeller U, Kuhn HJ. Postpartum erythrophagocytosis, iron storage and iron secretion in the endometrium of the tree shrew (Tupaia) during pregnancy. J Anat 1994;184:597e606. [40] Huxley TH. On the application of the laws of evolution to the arrangement of the Vertebrata, and more particularly of the Mammalia. Proc Zool Soc Lond 1880;43:649e62. [41] Murphy WJ, Eizirik E, Johnson WE, Zhang YP, Ryder OA, O’Brian SJ. Molecular phylogenetics and the origins of placental mammals. Nature 2001;409:614e8. [42] Carter AM. Evolution of the placenta and fetal membranes seen in the light of molecular phylogenetics. Placenta 2001;22:800e7. [43] Mess A, Carter AM. Evolutionary transformations of fetal membrane characters in Eutheria with special reference to Afrotheria. J Exp Zool (Mol Dev Evol) 2006;306B:140e63. [44] Mess A, Carter A. Review: evolution of the placenta during early radiation of placental mammals. Comp Biochem Physiol A Mol Integrat Physiol 2007;148: 769e79. [45] Martin RD. Evolution of placentation in Primates: implications of mammalian phylogeny. Evol Biol 2008;35:125e45. [46] Wildman DE, Chen C, Erez O, Grossman LI, Goodman M, Romero R. Evolution of the mammalian placenta revealed by phylogenetic analysis. Proc Natl Acad Sci USA 2006;103:3203e8. [47] Elliot MG, Crespi BJ. Phylogenetic evidence for early hemochorial placentation in Eutheria. Placenta 2009;30:923e1004. [48] Vogel P. The current molecular phylogeny of Eutherian mammals challenges previous interpretations of placental evolution. Placenta 2005;26:591e6.