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Comparative morphogenesis and vascular relationships of the villous hemochorial placenta
Comparative
morphogenesis
relationships
of the villous hemochorial
RALPH Brooklyn,
M. New
WYNN,
and
placenta
M.D.
York
S T u n 1 E s of placental transfer in experimental animals and man have added urgently practical importance to the academically stimulating aspects of comparative placentology. The purpose here is not to duplicate the comprehensive accounts of Mossman13 and Amoroso,l or the more recent synoptic reviews of Amoroso2-” and Wimsatt,‘” but rather to focus on the hemochorial placenta, upon which important physiological and biochemical experiments have been based. In particular, the histological variations among placentas of the hemochorial type, ranging from the typical labyrinthine architecture of the rodents to the free villous condition of the hominids, and the maternal-fetal circulatory relationships will be compared and contrasted in an effort to assess the validity of intergeneric extrapolation of data derived from laboratory investigations. Additional fine structural data, derived from electron microscopic studies, will be presented in a subsequent report. Materials
and vascular
recovered after normal vaginal delivery. The tissues were fixed in phosphate buffered 10 per cent formalin, embedded in paraffin and sectioned at 5~*, prior to staining with hematoxyiin and eosin and a variety of special stains. The placentas of the rat, rabbit and guinea pig, obtained at the time of autopsy of the full-term animals, were similarly fixed, sectioned, and stained. Sections of the placenta of the ninebanded armadillo (Dasypus novemcinctus) were prepared by Dr. A. C. Enders from tissues fixed in Carnoy’s fluid and sectioned at 7~. The photographs of the scaly-tailed squirrel (Anomalurus s,!J.) were made by Professor E. C. Amoroso from serially sectioned full-term placentas in his laboratory. The photomicrographs of the placenta of the spotted hyena (Crocuta crocuta) are based on studies of 5 specimens representing periods from the first third of pregnancy to full term. These placentas were fixed in formalin, section at 5 to 7,~ and subjected to a battery of stains. The examination of the specimens of Crocuta was performed in the course of study in Professor Amoroso’s laboratory at the Royal Veterinary College, London.
methods
First trimester and full-term human placental tissues were obtained at the time of curettage and cesarean section, respectively. Full-term placentas of the New World “squirrel monkey” (Saimiri sciureus) were obtained at autopsy; those of the Old World “bonnet monkey” (Macaca radiata) were
Observations
Hemochorial labyrinth. The placentas of the rat, rabbit, and guinea pig, representatives of the Myomorpha, Lagomorpha, and Hystricomorpha, respectively, demonstrate the maximal expression of the labyrinthine modification of the hemochorial conditi0n.l. I3 In the labyrinth the maternal blood
From the Department of Obstetrics and Gynecology, State University of New York, Downstate Medical Center. 758
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Villous
hemochorial
circulates in
narrow channels lined exclusively by trophoblast. Although no maternal endothelium persists, the slitlike spaces between the trophoblastic tubules correspond to the maternal capillaries of endotheliochorial labyrinths, such as those of the carnivores. In the rat (Fig. 2) and rabbit (Fig. 1), free villi are not found, but the histologic barrier between fetal and maternal blood is reduced to a thin rim of trophoblast, minimal fetal connective tissue and the capillary wall. With the light microscope it is often impossible to define precisely the nature and origin of the placental barrier. In the specialized placenta of the guinea pig (Fig. 3)) two types of labyrinthine trophoblast are distinguished, a fine syncytium with fetal capillaries and circulating maternal blood, and a coarse variety from which fetal vessels are absent. In general, the maternal arterial blood in the labyrinthine placenta flows toward the fetal surface of the placental disc, while the maternal venous blood returns through capillary-like spaces to the base. The fetal blood flow is in the opposite direction, in accord with the principle of countercurrent circulation first enunciated by Mossman12 in a study of the rabbit’s placenta. Anthropoid
placenta
Homo. In both early and full-term human placentas the villous hemochorial condition appears well developed. In the maternal blood spaces, which are wide sinuses rather than narrow slits, villi project freely. Except for a few villi that anchor in the basal decidua, most of the trophoblastic projections from the chorionic plate branch repeatedly and terminate freely in the intervillous space. Even in the early human placenta (Fig. 4) syncytial connections between adjacent terminal villous branches are sparse. A “layer” of cytotrophoblast is obvious even with light microscopy at this stage in the development of the villi, which are large and not well vascularized. At term (Fig. 5), the small terminal villi exhibit numerous syncytial knots, but intervillous connections are effected not by viable trophoblastic syn-
placenta-morphogenesis
and vascular
relation
759
cytium, but by fibrinous adhesions resulting from the organization of minute hematomas arising from occluded fetal vessels. In the absence of vascular connections between adjacent villi, the human placenta differs from that of some platyrrhine monkeys. Saimiri. Superficially quite different from the typically villous placenta of man is that of the New World “squirrel monkey,” Saimiri sciureus (Fig. 6). The villi branch extensively with concomitant reduction in the size of the terminal divisions, which are formed of fine connective tissue cores, covered by a layer of syncytial trophoblast, in which abundant capillaries lie quite close to the surface. In places, a villous pattern is found, whereas syncytial connections between adjacent villi convert most of the placental mass to a pseudolabyrinthine condition. The junctions may be long and slender, or short and thick, effecting intervillous connections in end-to-end, end-to-side, or side-to-side fashion. Exaggerated development of the syncytial bridges creates a trabecular pattern of maternal blood spaces of varying size and shape. Subsequent disruption of the intervillous connections converts the trabeculae in the affected areas to villi. Secondary connections formed by fibrinoid, as in the case of the human placenta, are also seen occasionally. Macaca. Sharing placental morphological characteristics of both Saimiri and Homo, the Old World “bonnet monkey,” Macaca radiata (Fig. 7), possesses a greater freedom of individual villi than Saimiri, but more intervillous fusions than Homo. Syncytial sprouts are prominent, moreover, although direct vascular connections between major villi are absent. Histologically the primary and secondary placentas are essentially identical. Whereas in the depths of the placenta syncytial junctions create a trabecular network with the intervillous space reduced to irregular clefts, many areas, particularly in the superficial zone, are typically villous, with wide maternal blood spaces almost indistinguishable from those of man. The definitive catarrhine placenta is, in effect, transitional histologically from the
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November 15, 1!364 Am. J. Obst. & Gym.
Fig. 1. Hemochorial labyrinth of the rabbit. Maternal blood circulates between trophoblastic lamellae. (X50). Fig. 2. Labyrinth of the rat. Maternal erythrocytes (E), circulate in the interstices of a network formed of trophoblastic tubules (7’). (x375). Fig. 3. Labyrinth of the guinea pig, showing coarse syncytium (CS), from which fetal vessels are absent, and fine syncytium (FS). (x220). Fig. 4. Entirely villous early human placenta. Syncytial junctions are rare. The double covering of epithelium is seen to consist of cytotrophoblast (L), and syncytium (S). (~125).
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90 6
Villous
hemochorial
placenta-morphogenesis
and
vascular
relation
Fig. 5. Full-term human placenta showing syncytial knots (K), and fibrinous deposits (F). The terminal villi are still essentially free. ,Fetal capillaries approach epithelium quite closely. (x250). Fig. 6. Transitional hemochorial placenta of the squirrel monkey, showing individual villi connected by abundant intervillous syncytium (IVS) , creating a pseudolabyrinthine configuration. (~125). Fig. 7. Hemochorial villous placenta of the bonnet monkey, showing syncytial knots (K), of individual villi approaches that in the human and intervillous junctions (I). Th e f reedom placenta (Figs. 4 and 5). (x250). placenta of the hyena. Syncytial junctions are frequently Fig. 8. Villous or “semivillous” seen (1). A more trabecular labyrinthine arrangement (L) creates a close resemblance in certain areas to the condition in the New World monkeys (Fig. 6). (x250).
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Fig. 9. Villous placenta of the scaly-tailed squirrel, showing origin of the villi from the chorionic plate (CP). Syncytial junctions are prominent (J ). The general villous pattern closely resembles that of the anthropoids. (x75). Fig. 10. Placenta of the scaly-tailed squirrel demonstrating anchoring villi (,4), and a highly developed deciduai reaction (D) . (x75 ) . Fig. 11. Placenta of the armadillo showing endometrial gland (E). and several branched and anastomosing villi with cytotrophoblastic cell columns at their tips (CC). (x125). Fig. 12. Villus of the armadillo, with epithelium consisting solely of syncytiotrophoblast (A’). The cytotrophoblast is confined to the cell columns at the tips (C). Fetal capillaries closely approach the syncytium, but do not indent it. Fibroblasts in the mesenchymal cores are promi. nent. (X250).
Villous
hemochorial
placenta-morphogenesis
and
vascular
relation
Fig. 13. Placenta of hyena from about mid-gestation. The double-layered trophoblast is seen to consist of Langhans cells (L) and syncytiotrophoblast (T) . (x1000). Fig. 14. Villus from full-term placenta of the hyena, showing fetal capillaries (ZE) indenting the syncytial covering and assuming an almost intraepithelial position. (x880). Fig. 15. Margin of the placenta of the hyena, demonstrating the course of the maternal artery (A), through a crescent of endometrial tissue, to direct entrance into the subchorial sinus (at arrow). (X25). Fig. 16. Venous drainage at the base of the placenta of the hyena. Three tributaries join to form a large basal vein (BV) . (~45). Fig. 17. Diagram from Bumm,’ showing his concept of the placental circulation. High septal entry of the arteries (A), into the intervillous space (ZVS), and basal venous drainage (Blr), are shown. Although the human placental circulation differs significantly, that of the hyena shows striking similarities to Bumm’s model.
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pseudolabyrinth entirely villous
of the pIatyrrhines to the human placenta. Anomalurus. The scaly-tailed squirrel, Anomalurus, possesses a hemochorial placenta in which the villi have a remarkable degree of freedom. The chorionic plate gives rise to slender villi that branch and ramify (Fig. 9) ; also prominent are villi that anchor in an endometrium characterized by a well-developed decidual reaction and numerous giant cells (Fig. 10). The individual villi arc covered throughout their length by what appears under the light microscope to be syncytial trophoblast. The uterine artery discharges directly into the intervillous space at its base, much as in the case of the monkey. Dasypus. The definitive placenta of the nine-banded armadillo, Dar-~l~~us nouemcinctus, also is hemochorial, with the highly branched and anastomotic villi forming a spongework (Fig. 11) . The unusual vascular villi, arising as protrusions from the chorionic plate, are covered by syncytial trophoblast alone, with cytotrophoblast restricted to the distal extremities as cell columns (Fig. 12). Langhans cells and anchoring villi arc absent. Fibroblasts are prominent in the connective tissue cores, as are fetal capillaries, which assume a position close to, but not indenting, the trophoblastic epithelium. Enders” has interpreted the structure of the villi. the position of the cell columns and the restriction of mitotic activity to the cytotrophoblast as evidence that the syncytium arises solely from cellular trophoblast throughout the period of growth of the vilii. lnterruption of the endometrial blood sinuses forms a pool of blood into which the villi project. The maternal blood flow, as described by Enders,” is unidirectional, entering the sinuses under arches of endometrial tissue and proceeding toward the muscular \vall. In the anthropoids, on the other hand. blood both enters and leaves through the basal plate, as detailed by Ramsey.14! I5 Both Anomalurus and Dasypus have in addition to their chorioallantoic placentas comples inverted yolk sacs; in both these forms histotrophic adaptions are more marked than in man and Old World monkeys. In the
New World monkeys, and in the hyena, described below, there is again greater dependence on histotrophic, as opposed to lremotrophic, functions. Crocuta. The nondeciduate placenta of the spotted hyena, Crocuta crocuta, in its retention to term of a moderately sized noninverted yolk sac and a permanent large allantois, resembles that of the carnivores in general.“” Its hemochorial villous or semivillous architecture (Fig. 8 j, however, resembles more closely that of the New World monkeys t1la.n of the other carnivores, which possess typically labyrinthine endotheliochorial placentas. The inner surface of the chorionic plate is covered by allantoic cndoderm and its outer surface by syncytial trophobtast, which constitutes the epithelium of vascular cliorioallantoic projections. The stem villi divide repeatedly as they cross the Yabyrinth,“ in places forming a spon,gework of trabeculae, as in the placenta of Saimiri, and in other areas exhibiting the freedom of individual villi characteristic of Homo and Macaca. The villous epithelium comprises taco types of trophoblast, an outer syncytium and an inner Langhans layer (Fig. 13). Fetal capillaries approach the surface so closely as to indent the syncytial troplioblast (Fig. 14:). assuming an almost iritracpitheliai location: the histologic barrier between fetal and maternal red cells is thus ICcluced to what appears, under the light microscope, as a markedly attenuated lavcr of syncytial trophoblast, a minimurn of connecti\,e tissue and the fetal capillary wall. Different from most carnivores, tlrc h!-ma possesses no placental hematoma or marginal deposit of piptuent, although paraplaccntal cytotroplroblast under-go stl.lic.~lll-Itl does modifications associated with pha~oc~~rosis of histotroph. Placrntatiori in (:rocuta is of furthci. iiitercst lvith n-gard to tbc maternal circrrlation.‘.+. ” The main uterine arterial branch is carried up in a crescent of endomettial tissue at the margin of the placenta to onpty directly into the subchorial sinus 1Fi,g. 1.5) . a syncytium-lined space cstcndinz across the entire placental face. Smaller
Volume Number
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Villous
hemochorial
arteries reach the sinus in maternal septa that traverse the trophoblastic zone. Major arteries do not discharge blood at the base of the placenta, but basal drainage constitutes the sole means of return of blood to the uterine veins (Fig. 16). The margin of the placenta is deeply undercut by a double fold of allantochorion in a fashion simulating true circumvallation, but differing in the applications of fetal membranes to both endometrial and placental surfaces deep into the angle of separation. The crescentic band of gestational endometrial tissue is carried up along the free edge of the placental wedge, providing a framework along which the maternal arteries are brought to their point of communication with the subchorial sinus, from which blood seeps into the intervillous space through numerous apertures. The wall of the maternal artery terminates abruptly at its junction with the sinus. Unlike the subchorial “lake” of Spanner,ls the sltbchorial sinus of the hyena receives arterial blood. In the high septal entry of maternal blood and the exclusively basal venous return, the circulation in Crocuta resembles the human model of Bumm7 (Fig. 17)) and represents certain improvements in efficiency of countercurrent flow. Comment
Formation of the hemochorial villous placenta. In his recent review, WimsatP pointed out that villi may arise primarily as outgrowths from the chorionic membrane, or secondarily from the basal plate as prot rusions of cytotrophoblast that grow into a preformrd syncytial mantle, as in the case of the bat Myotis lucifugus. The initially solid villous protrusions are subsequently vascularized by the ingrowth of allantoic tnesench>me and vessels. On the one hand, although the deferred formation of villi usually results in the labyrinthine condition, the human placenta, according to Hamilton and Royd,g is derived from an earlier labyrinthine stage, and, conversely, the lamelliform placenta of the carnivores is a secondary modification of the originally villous condition, brought about by fusion of the small
placenta-morphogenesis
and
vascular
relation
765
villous branches of the chorion, as described by Wislocki and Dempsey.‘2 When the trophoblastic syncytium, or plasmodium, according to Mossman,13 surrounds the maternal vessels, which soon thereafter lose their endothelium, a temporary endotheliochorial condition precedes the development of the hemochorial state. Further invasion and piling up of the plasmodium transform the early villi into a labyrinth. If the trophoblast initially ruptures the maternal vessels with the escape of blood to form large sinuses, trabeculae are formed across the blood-filled spaces, rather than lamellae between them, and a villous rather than a labyrinthine condition results. Wislocki’s studies of the marmoset,2o the macaque,23 and the evolutionary history of the primates in genera1,21 demonstrate clearly the transition from the labyrinth of the New World monkeys to the typical villous condition of the placenta of man and the great apes. Hill’slO explanation of the basic diffcrence between the labyrinth of the platyrrhines and the villous condition of the Old World monkeys and man rests on the differential activity of the ectoplacental trophoblast. In the platyrrhines there is from the beginning a broad attachment to the endometrium that provides early and massive proliferation of trophoblast. Instead of cell columns or a cytotrophoblastic shell, there are irregular coarse anastomotic processes of the peripheral syncytium. The intervillous syncytium, converting the villi into trabeculae, gradually decreases as a result of fibrinoid degeneration, and, as additional free villi are formed, a condition closely resemblin, 0 that of the catarrhines arises. In the catarrhines, according to Hill,l” the trophoblast is endowed with more potent invasive properties from the beginning, and chorionic villi lie free in the intervillous space in contact with maternal blood almost as soon as they are formed. There is thus a less massive primary trophoblastic proliferation, and the expanded fused tips of the cell
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columns spread out as a thin sheet of cytotrophoblast in the junctional zone, corresponding to the trophoblastic shell of the human embryo. Wislocki” and Wislocki and StreeterZ3 believed that the syncytial connections in the catarrhine placenta represented the remains of an originally profuse intervillous syncytium, but HillI” regarded them as arising late as sprouts of the syncytium, which has the capacity to form localized proliferations throughout placental development. Wislocki and Streeter held, furthermore, that the manner and growth of the trophoblast in the formation of the placenta depend to a large extent on the character of the endometrial reaction. They regarded the information obtained from study of deciduomata as indicating that Hill’s concept of placental evolution depended too exclusively on the trophoblast. In considering the typical endotheliochorial labyrinth of the carnivores, Mossmanl” suggested that its hematoma was analogous to the hemochorial villous state, but Wynn and AmorosoZ5 preferred not to consider the stagnant pools of blood, representing hemorrhage through an intact uterine epithelium, as comparable; only in the case of the hyena, among the carnivores, is a true hemochoria1 situation found. Here the resemblance to the placenta of the New World monkeys is striking. Evolutionary considerations. The hemochorial placenta is found in a variety of unrelated animals. Labyrinthine architecture characterizes the placenta of some insectivores, lagomorphs, most rodents, many Chiroptera, the hyracoids, and sirenians.l” The hemochorial villous state is found in the insectivora (Tenrecidae) ,I0 among all three suborders of the Anthropoidea,‘, lo, ” among the edentates (Dasypodidae and Myrmecophagidae) , 8 and among the rodents in the Anomaluroidea.6 Principles of parallel evolution must be operative, for it seems highIy unhkeIy that phylogenetic reiationships can be established among all animals with hemochorial placentas. Although the recent exceptions to the interordinal relationships postulated in Mossman’s stimulating
November
15, 1964
Am. J. Obst. L Gynec.
monograph fail to detract from its genera1 value, the occurrence of the hemochorial placenta in some of the more primitive and less specialized mammals casts serious doubt on the validity of the Grosser concept, supported by Hill,l” of the modern epitheliochorial placenta as the ancestral type. Evidence supports instead the theories of Wislockizl and Mossma.n,l” that relegate the endotheliochorial and hemochorial labyrinths to primitive status. It is interesting that, except for the anthropoids and insectivores, most of the animals with hemochorial villous placentas occupy rather isolated taxonomic positions. According to Simpson,Z” the Hyaenidae, much the smallest family of carnivores, are a late (Miocene) offshoot of the viverrids, representing a somewhat aberrant group. The nine-banded armadillo, too, occupies a rather isolated position in the Dasypodini among the Dasypodoidea. Mossman,l” in fact, regards their fetal membranes as the most aberrant of any mammalian group because of their polyembryony, their hemochorial villous placenta resembling that of the anthropoids, the early and complete inversion of the yolk as in the higher Rodentia, and the MC, orientation of the disc and first attachment to the uterus just the opposite of that in the rodents. With regard to the classification of the Anomaluroidea, Simpson’6 places them with the sciuromorphs, fautp dc micux, considering them “the most dubious members of the dubious order.” -4ttempts to establish evolutionary relationships according to the presence and variety of hemochorial placenta are further thwarted by the striking resemblance of the mid-gestational and full-term placenta of thr hyena to the mature placenta of the New World monkeys. A generalization that appears more plausible on the basis of the descriptions here set forth is that the hemochorial condition, having probably arisen independentIy in severa unreIated mammalian groups, results in each case from extensive erosion of maternal vessels associated with suppression of maternal capillary growth; the labyrinthine and villous condi-
V&me Number
90 6
Villous
hemochorial
tions, furthermore, are not fundamentally different, the breakdown of syncytial connections converting the former to the latter, and the lamellae to villi. Circulatory relationships. When Mossmanl” described the opposing directions of flow of the fetal and maternal blood in the labyrinth of the rabbit, he established a principle of countercurrent flow in the placenta, whereby reduced fetal blood first contacts venous and then increasingly arterialized maternal blood. Basic agreement followed in recognizing the principle in both hemoand endotheliochorial labyrinths, but in the case of the hemochorial villous placentas, such as those of the anthropoids, there was no such unanimity. Ramsey141 I5 has summarized the thinking that preceded her elucidation of the physiological theory of the human placental circulation. Bumm’* 24 wrote that maternal blood entered the intervillous space near the summits of maternal septa and that the venous return was entirely basal. SpanneP denied the random distribution of arteries and veins, stating that the venous return from the placenta was exclusively marginal. Stieve17 disagreed with both Bumm and Spanner, suggesting that all primate placentas, including that of man, were basically labyrinthine, comprising an intercommunicating network formed by the fusion of villous tips, with fetal vessels running uninterruptedly from one villus to another. Kline*l later showed that the apparent intervillous connections were, in fact, results of the organization of minute hematomas caused by the occlusion of fetal blood vessels, and that direct vascular connections were nonexistent. In comparing the circulation of the maternal blood in the mature placenta of the platyrrhine monkey with that in the typical labyrinth, HilP noted a very close similarity in the entry of arterial blood through septa and the exit through the base. Ramsey extended the analogy to include the villous placenta, regarding the amorphous blood lake as a substitute for closed maternal capillary channels. She suggested that the separation of the afferent and
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eff erent bloodstreams was accomplished by pressure differentials rather than by morphologic factors. In the villous hemochorial placentas of both the armadillo and the hyena, considerable improvement in the mechanics of countercurrent flow is achieved, albeit by rather different vascular adaptations. In the armadillo invasion of the maternal blood sinuses with subsequent enlargement by the villi to form the intervillous space is the unique feature of placentation, according to Enders.* The maternal vascular system in Dasypus is uninterrupted except at the fundus and the consequent blood flow is unidirectional. Since the maternal blood &ters the sinuses under the endometrial arches, thence flowing toward the muscular layer, relatively less mixing of oxygenated and reduced blood occurs than in the intervillous spaces of man and Old World monkeys, in which blood both enters and leaves through the basal plate. The fetal blood vessels, too, enter the intervillous space near the luminal border of the placenta and the venous return is from the muscular wall toward the lumen. The result is a rough countercurrent, with more highly oxygenated fetal blood near the surface. Enders makes the significant qualification, in the case of the armadillo, that direct countercurrent flow is precluded by the random distribution of the highly branched and anastomotic villi, which form a rather complicated spongework. In the the direction of fetal capillaries, therefore, blood flow bears no fixed relationship to that of the maternal flow. In the case of the spotted hyena it is significant that the maternal arterial blood is discharged not at the basal plate into the intervillous space, as in man and the macaque, but high in the fetal portion of the placenta at or near the summits of complete maternal septa, and that the venous blood is returned to the uterine veins solely at the placental base, as in the case of the New World monkeys and most carnivores, which possess labyrinthine placentas. The placental circulation in Crocuta thus resembles closely the human model proposed by Bumm, while
768 Wynn
differing greatly from what has since been learned of the human circulation through Ramsey’s research. Although Enders’ comments regarding Dasypus are somewhat applicable to Crocuta as well, the complete septa and the less randomly oriented terminal villi of the hyena create the closest approximation to ideal countercurrent flow that has been demonstrated in any villous placenta thus far examined. Summary
and
conclusions
1. Hemochorial villous placentas of man. Old World and New World monkeys, the armadillo and the scaly-tailed squirrel are histologically described and compared. 2. Modes of origin of the hemochorial condition in the various mammalian Orders and the transitional stagesfrom labyrinthine to villous placentas are described. 3. Direct phylogenetic relationships among the diverse mammals with hemochorial placentas are denied. 4. The histological “barrier” varies among
villous hemochorial placental types, Absence of Langhans cells in the armadillo and “intraepithelial” capillaries in the hyena minimize the thickness of the histological barrier in the respective species. 5. Vascular adaptations likewise vary, with approximate, and almost ideal, countercurrent flow found in Dasypus and Crocuta, respectively. 6. Morphologic variants among hemochorial placentas suggestcaution in the intergeneric extrapolation of physiologic data.
Dr. .4llen (:. Enders,Departnrent of Anatomy, Washington.University School of Medicine, St. Louis, Missouri, generouslysupplieda sectionof the placenta of Dasypusnovemcinctus.Professor E. C. Amoroso, Department of Physiology, Royal Veterinary Collrgc, IJniversity of London, not only provided the photomicrographs of placenta of Anomalurus, but made available the author the facilities of his department, which the study of Crocufn crocuta was formed.
the to in per-
REFERENCES
1. Amoroso, E. C.: In Parkes, A. S., editor: Marshall’s Physiology of Reproduction, London, 1952, Longmans, Green & Co., Inc., vol. ‘) p. 127. 2. &~oroso, E. C.: In Flexner, L. C., editor: Gestation, Tr. of the First Conference, New York, 1954, Josiah Macy, Jr. Foundation, p. 1’19. 3. Amoroso, E. C.: In Villee, C. A., editor: Gestation, Tr. of the Fifth Conference, New York, 1958, Josiah Macy, Jr. Foundation, p. 15. -4. Amoroso, E. C.: Ann. New York Acad. SC. 75: 855, 1959. 5. Amoroso, E. C.: Brit. M. Bull. 17: 1, 1961. 6. Branca, A.. and Cretin, A.: Compt.-rend. Assoc.anat. 20: 139, 1925. 7. Bumm, E.: Arch. GynHk. 43: 181, 1893. 8. Enders, A. C.: J. Anat. 94: 34, 1960. 9. Hamilton, W. J., and Boyd, J. D.: J. Anat. 94: 297, 1960. 10 Hill, J. P.: Phil. Tr. Roy. Sot. London, Series B. 221: 45. 1932. 11. Kline, B. S.: A&. 5. OBST. & GYNEC. 61: 1065,- 1951. H. W.: Am. J. Anat. 37: 433, 1926. 12. Mossman,
13. 14. 15. 16. 17. 18. 19. 20. 21. ‘,‘J *-. ‘3. 24 25.
Mossman, H. W.: Contrib. Embryol. 26: 129. 1937. Ramsey, E. M.: Ann. New York Acad. SC. 75: 726, 1959. Ramsey, E. M.: Au. J. OBST. & GYNEC. 84: 1649. 1962. Simpson, G. G.: Bull. Am. Mus. Nat. Hist. 85: 1, 194.5. Stieve, H.: Zentralbl. Gynak. 65: 370, 1941. Spanner, R.: Ztschr. Anat. 105: 163, 1935. Wimsatt, W. A.: .4&r. J. OBST. & Guxec. 84: 1568, 1962. Wislocki, G. B.: Anat. Rec. 52: 381, 1932. Wislocki, G. B.: Contrib. Embrvol. 20: 51. 1929. Wislocki, G. B.. and Dempsey, E. W.: Am. J. Anat. 78: 1. 1946. Wislocki, G. B., and Streeter, G. I,.: Gontrib. Embryo]. 27: 1, 1938. Wynn, R. M.: AM. J. OBST. & GYNEC. 87: 829, 1963. Wynn, R. M., and Amoroso, E. C:.: .4m. J. Anat. (In press.) 450 Clarkson Avenue Brooklvn 3. New York
morphogenesis
relationships
of the villous hemochorial
RALPH Brooklyn,
M. New
WYNN,
and
placenta
M.D.
York
S T u n 1 E s of placental transfer in experimental animals and man have added urgently practical importance to the academically stimulating aspects of comparative placentology. The purpose here is not to duplicate the comprehensive accounts of Mossman13 and Amoroso,l or the more recent synoptic reviews of Amoroso2-” and Wimsatt,‘” but rather to focus on the hemochorial placenta, upon which important physiological and biochemical experiments have been based. In particular, the histological variations among placentas of the hemochorial type, ranging from the typical labyrinthine architecture of the rodents to the free villous condition of the hominids, and the maternal-fetal circulatory relationships will be compared and contrasted in an effort to assess the validity of intergeneric extrapolation of data derived from laboratory investigations. Additional fine structural data, derived from electron microscopic studies, will be presented in a subsequent report. Materials
and vascular
recovered after normal vaginal delivery. The tissues were fixed in phosphate buffered 10 per cent formalin, embedded in paraffin and sectioned at 5~*, prior to staining with hematoxyiin and eosin and a variety of special stains. The placentas of the rat, rabbit and guinea pig, obtained at the time of autopsy of the full-term animals, were similarly fixed, sectioned, and stained. Sections of the placenta of the ninebanded armadillo (Dasypus novemcinctus) were prepared by Dr. A. C. Enders from tissues fixed in Carnoy’s fluid and sectioned at 7~. The photographs of the scaly-tailed squirrel (Anomalurus s,!J.) were made by Professor E. C. Amoroso from serially sectioned full-term placentas in his laboratory. The photomicrographs of the placenta of the spotted hyena (Crocuta crocuta) are based on studies of 5 specimens representing periods from the first third of pregnancy to full term. These placentas were fixed in formalin, section at 5 to 7,~ and subjected to a battery of stains. The examination of the specimens of Crocuta was performed in the course of study in Professor Amoroso’s laboratory at the Royal Veterinary College, London.
methods
First trimester and full-term human placental tissues were obtained at the time of curettage and cesarean section, respectively. Full-term placentas of the New World “squirrel monkey” (Saimiri sciureus) were obtained at autopsy; those of the Old World “bonnet monkey” (Macaca radiata) were
Observations
Hemochorial labyrinth. The placentas of the rat, rabbit, and guinea pig, representatives of the Myomorpha, Lagomorpha, and Hystricomorpha, respectively, demonstrate the maximal expression of the labyrinthine modification of the hemochorial conditi0n.l. I3 In the labyrinth the maternal blood
From the Department of Obstetrics and Gynecology, State University of New York, Downstate Medical Center. 758
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circulates in
narrow channels lined exclusively by trophoblast. Although no maternal endothelium persists, the slitlike spaces between the trophoblastic tubules correspond to the maternal capillaries of endotheliochorial labyrinths, such as those of the carnivores. In the rat (Fig. 2) and rabbit (Fig. 1), free villi are not found, but the histologic barrier between fetal and maternal blood is reduced to a thin rim of trophoblast, minimal fetal connective tissue and the capillary wall. With the light microscope it is often impossible to define precisely the nature and origin of the placental barrier. In the specialized placenta of the guinea pig (Fig. 3)) two types of labyrinthine trophoblast are distinguished, a fine syncytium with fetal capillaries and circulating maternal blood, and a coarse variety from which fetal vessels are absent. In general, the maternal arterial blood in the labyrinthine placenta flows toward the fetal surface of the placental disc, while the maternal venous blood returns through capillary-like spaces to the base. The fetal blood flow is in the opposite direction, in accord with the principle of countercurrent circulation first enunciated by Mossman12 in a study of the rabbit’s placenta. Anthropoid
placenta
Homo. In both early and full-term human placentas the villous hemochorial condition appears well developed. In the maternal blood spaces, which are wide sinuses rather than narrow slits, villi project freely. Except for a few villi that anchor in the basal decidua, most of the trophoblastic projections from the chorionic plate branch repeatedly and terminate freely in the intervillous space. Even in the early human placenta (Fig. 4) syncytial connections between adjacent terminal villous branches are sparse. A “layer” of cytotrophoblast is obvious even with light microscopy at this stage in the development of the villi, which are large and not well vascularized. At term (Fig. 5), the small terminal villi exhibit numerous syncytial knots, but intervillous connections are effected not by viable trophoblastic syn-
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cytium, but by fibrinous adhesions resulting from the organization of minute hematomas arising from occluded fetal vessels. In the absence of vascular connections between adjacent villi, the human placenta differs from that of some platyrrhine monkeys. Saimiri. Superficially quite different from the typically villous placenta of man is that of the New World “squirrel monkey,” Saimiri sciureus (Fig. 6). The villi branch extensively with concomitant reduction in the size of the terminal divisions, which are formed of fine connective tissue cores, covered by a layer of syncytial trophoblast, in which abundant capillaries lie quite close to the surface. In places, a villous pattern is found, whereas syncytial connections between adjacent villi convert most of the placental mass to a pseudolabyrinthine condition. The junctions may be long and slender, or short and thick, effecting intervillous connections in end-to-end, end-to-side, or side-to-side fashion. Exaggerated development of the syncytial bridges creates a trabecular pattern of maternal blood spaces of varying size and shape. Subsequent disruption of the intervillous connections converts the trabeculae in the affected areas to villi. Secondary connections formed by fibrinoid, as in the case of the human placenta, are also seen occasionally. Macaca. Sharing placental morphological characteristics of both Saimiri and Homo, the Old World “bonnet monkey,” Macaca radiata (Fig. 7), possesses a greater freedom of individual villi than Saimiri, but more intervillous fusions than Homo. Syncytial sprouts are prominent, moreover, although direct vascular connections between major villi are absent. Histologically the primary and secondary placentas are essentially identical. Whereas in the depths of the placenta syncytial junctions create a trabecular network with the intervillous space reduced to irregular clefts, many areas, particularly in the superficial zone, are typically villous, with wide maternal blood spaces almost indistinguishable from those of man. The definitive catarrhine placenta is, in effect, transitional histologically from the
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November 15, 1!364 Am. J. Obst. & Gym.
Fig. 1. Hemochorial labyrinth of the rabbit. Maternal blood circulates between trophoblastic lamellae. (X50). Fig. 2. Labyrinth of the rat. Maternal erythrocytes (E), circulate in the interstices of a network formed of trophoblastic tubules (7’). (x375). Fig. 3. Labyrinth of the guinea pig, showing coarse syncytium (CS), from which fetal vessels are absent, and fine syncytium (FS). (x220). Fig. 4. Entirely villous early human placenta. Syncytial junctions are rare. The double covering of epithelium is seen to consist of cytotrophoblast (L), and syncytium (S). (~125).
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Fig. 5. Full-term human placenta showing syncytial knots (K), and fibrinous deposits (F). The terminal villi are still essentially free. ,Fetal capillaries approach epithelium quite closely. (x250). Fig. 6. Transitional hemochorial placenta of the squirrel monkey, showing individual villi connected by abundant intervillous syncytium (IVS) , creating a pseudolabyrinthine configuration. (~125). Fig. 7. Hemochorial villous placenta of the bonnet monkey, showing syncytial knots (K), of individual villi approaches that in the human and intervillous junctions (I). Th e f reedom placenta (Figs. 4 and 5). (x250). placenta of the hyena. Syncytial junctions are frequently Fig. 8. Villous or “semivillous” seen (1). A more trabecular labyrinthine arrangement (L) creates a close resemblance in certain areas to the condition in the New World monkeys (Fig. 6). (x250).
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Fig. 9. Villous placenta of the scaly-tailed squirrel, showing origin of the villi from the chorionic plate (CP). Syncytial junctions are prominent (J ). The general villous pattern closely resembles that of the anthropoids. (x75). Fig. 10. Placenta of the scaly-tailed squirrel demonstrating anchoring villi (,4), and a highly developed deciduai reaction (D) . (x75 ) . Fig. 11. Placenta of the armadillo showing endometrial gland (E). and several branched and anastomosing villi with cytotrophoblastic cell columns at their tips (CC). (x125). Fig. 12. Villus of the armadillo, with epithelium consisting solely of syncytiotrophoblast (A’). The cytotrophoblast is confined to the cell columns at the tips (C). Fetal capillaries closely approach the syncytium, but do not indent it. Fibroblasts in the mesenchymal cores are promi. nent. (X250).
Villous
hemochorial
placenta-morphogenesis
and
vascular
relation
Fig. 13. Placenta of hyena from about mid-gestation. The double-layered trophoblast is seen to consist of Langhans cells (L) and syncytiotrophoblast (T) . (x1000). Fig. 14. Villus from full-term placenta of the hyena, showing fetal capillaries (ZE) indenting the syncytial covering and assuming an almost intraepithelial position. (x880). Fig. 15. Margin of the placenta of the hyena, demonstrating the course of the maternal artery (A), through a crescent of endometrial tissue, to direct entrance into the subchorial sinus (at arrow). (X25). Fig. 16. Venous drainage at the base of the placenta of the hyena. Three tributaries join to form a large basal vein (BV) . (~45). Fig. 17. Diagram from Bumm,’ showing his concept of the placental circulation. High septal entry of the arteries (A), into the intervillous space (ZVS), and basal venous drainage (Blr), are shown. Although the human placental circulation differs significantly, that of the hyena shows striking similarities to Bumm’s model.
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pseudolabyrinth entirely villous
of the pIatyrrhines to the human placenta. Anomalurus. The scaly-tailed squirrel, Anomalurus, possesses a hemochorial placenta in which the villi have a remarkable degree of freedom. The chorionic plate gives rise to slender villi that branch and ramify (Fig. 9) ; also prominent are villi that anchor in an endometrium characterized by a well-developed decidual reaction and numerous giant cells (Fig. 10). The individual villi arc covered throughout their length by what appears under the light microscope to be syncytial trophoblast. The uterine artery discharges directly into the intervillous space at its base, much as in the case of the monkey. Dasypus. The definitive placenta of the nine-banded armadillo, Dar-~l~~us nouemcinctus, also is hemochorial, with the highly branched and anastomotic villi forming a spongework (Fig. 11) . The unusual vascular villi, arising as protrusions from the chorionic plate, are covered by syncytial trophoblast alone, with cytotrophoblast restricted to the distal extremities as cell columns (Fig. 12). Langhans cells and anchoring villi arc absent. Fibroblasts are prominent in the connective tissue cores, as are fetal capillaries, which assume a position close to, but not indenting, the trophoblastic epithelium. Enders” has interpreted the structure of the villi. the position of the cell columns and the restriction of mitotic activity to the cytotrophoblast as evidence that the syncytium arises solely from cellular trophoblast throughout the period of growth of the vilii. lnterruption of the endometrial blood sinuses forms a pool of blood into which the villi project. The maternal blood flow, as described by Enders,” is unidirectional, entering the sinuses under arches of endometrial tissue and proceeding toward the muscular \vall. In the anthropoids, on the other hand. blood both enters and leaves through the basal plate, as detailed by Ramsey.14! I5 Both Anomalurus and Dasypus have in addition to their chorioallantoic placentas comples inverted yolk sacs; in both these forms histotrophic adaptions are more marked than in man and Old World monkeys. In the
New World monkeys, and in the hyena, described below, there is again greater dependence on histotrophic, as opposed to lremotrophic, functions. Crocuta. The nondeciduate placenta of the spotted hyena, Crocuta crocuta, in its retention to term of a moderately sized noninverted yolk sac and a permanent large allantois, resembles that of the carnivores in general.“” Its hemochorial villous or semivillous architecture (Fig. 8 j, however, resembles more closely that of the New World monkeys t1la.n of the other carnivores, which possess typically labyrinthine endotheliochorial placentas. The inner surface of the chorionic plate is covered by allantoic cndoderm and its outer surface by syncytial trophobtast, which constitutes the epithelium of vascular cliorioallantoic projections. The stem villi divide repeatedly as they cross the Yabyrinth,“ in places forming a spon,gework of trabeculae, as in the placenta of Saimiri, and in other areas exhibiting the freedom of individual villi characteristic of Homo and Macaca. The villous epithelium comprises taco types of trophoblast, an outer syncytium and an inner Langhans layer (Fig. 13). Fetal capillaries approach the surface so closely as to indent the syncytial troplioblast (Fig. 14:). assuming an almost iritracpitheliai location: the histologic barrier between fetal and maternal red cells is thus ICcluced to what appears, under the light microscope, as a markedly attenuated lavcr of syncytial trophoblast, a minimurn of connecti\,e tissue and the fetal capillary wall. Different from most carnivores, tlrc h!-ma possesses no placental hematoma or marginal deposit of piptuent, although paraplaccntal cytotroplroblast under-go stl.lic.~lll-Itl does modifications associated with pha~oc~~rosis of histotroph. Placrntatiori in (:rocuta is of furthci. iiitercst lvith n-gard to tbc maternal circrrlation.‘.+. ” The main uterine arterial branch is carried up in a crescent of endomettial tissue at the margin of the placenta to onpty directly into the subchorial sinus 1Fi,g. 1.5) . a syncytium-lined space cstcndinz across the entire placental face. Smaller
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arteries reach the sinus in maternal septa that traverse the trophoblastic zone. Major arteries do not discharge blood at the base of the placenta, but basal drainage constitutes the sole means of return of blood to the uterine veins (Fig. 16). The margin of the placenta is deeply undercut by a double fold of allantochorion in a fashion simulating true circumvallation, but differing in the applications of fetal membranes to both endometrial and placental surfaces deep into the angle of separation. The crescentic band of gestational endometrial tissue is carried up along the free edge of the placental wedge, providing a framework along which the maternal arteries are brought to their point of communication with the subchorial sinus, from which blood seeps into the intervillous space through numerous apertures. The wall of the maternal artery terminates abruptly at its junction with the sinus. Unlike the subchorial “lake” of Spanner,ls the sltbchorial sinus of the hyena receives arterial blood. In the high septal entry of maternal blood and the exclusively basal venous return, the circulation in Crocuta resembles the human model of Bumm7 (Fig. 17)) and represents certain improvements in efficiency of countercurrent flow. Comment
Formation of the hemochorial villous placenta. In his recent review, WimsatP pointed out that villi may arise primarily as outgrowths from the chorionic membrane, or secondarily from the basal plate as prot rusions of cytotrophoblast that grow into a preformrd syncytial mantle, as in the case of the bat Myotis lucifugus. The initially solid villous protrusions are subsequently vascularized by the ingrowth of allantoic tnesench>me and vessels. On the one hand, although the deferred formation of villi usually results in the labyrinthine condition, the human placenta, according to Hamilton and Royd,g is derived from an earlier labyrinthine stage, and, conversely, the lamelliform placenta of the carnivores is a secondary modification of the originally villous condition, brought about by fusion of the small
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765
villous branches of the chorion, as described by Wislocki and Dempsey.‘2 When the trophoblastic syncytium, or plasmodium, according to Mossman,13 surrounds the maternal vessels, which soon thereafter lose their endothelium, a temporary endotheliochorial condition precedes the development of the hemochorial state. Further invasion and piling up of the plasmodium transform the early villi into a labyrinth. If the trophoblast initially ruptures the maternal vessels with the escape of blood to form large sinuses, trabeculae are formed across the blood-filled spaces, rather than lamellae between them, and a villous rather than a labyrinthine condition results. Wislocki’s studies of the marmoset,2o the macaque,23 and the evolutionary history of the primates in genera1,21 demonstrate clearly the transition from the labyrinth of the New World monkeys to the typical villous condition of the placenta of man and the great apes. Hill’slO explanation of the basic diffcrence between the labyrinth of the platyrrhines and the villous condition of the Old World monkeys and man rests on the differential activity of the ectoplacental trophoblast. In the platyrrhines there is from the beginning a broad attachment to the endometrium that provides early and massive proliferation of trophoblast. Instead of cell columns or a cytotrophoblastic shell, there are irregular coarse anastomotic processes of the peripheral syncytium. The intervillous syncytium, converting the villi into trabeculae, gradually decreases as a result of fibrinoid degeneration, and, as additional free villi are formed, a condition closely resemblin, 0 that of the catarrhines arises. In the catarrhines, according to Hill,l” the trophoblast is endowed with more potent invasive properties from the beginning, and chorionic villi lie free in the intervillous space in contact with maternal blood almost as soon as they are formed. There is thus a less massive primary trophoblastic proliferation, and the expanded fused tips of the cell
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columns spread out as a thin sheet of cytotrophoblast in the junctional zone, corresponding to the trophoblastic shell of the human embryo. Wislocki” and Wislocki and StreeterZ3 believed that the syncytial connections in the catarrhine placenta represented the remains of an originally profuse intervillous syncytium, but HillI” regarded them as arising late as sprouts of the syncytium, which has the capacity to form localized proliferations throughout placental development. Wislocki and Streeter held, furthermore, that the manner and growth of the trophoblast in the formation of the placenta depend to a large extent on the character of the endometrial reaction. They regarded the information obtained from study of deciduomata as indicating that Hill’s concept of placental evolution depended too exclusively on the trophoblast. In considering the typical endotheliochorial labyrinth of the carnivores, Mossmanl” suggested that its hematoma was analogous to the hemochorial villous state, but Wynn and AmorosoZ5 preferred not to consider the stagnant pools of blood, representing hemorrhage through an intact uterine epithelium, as comparable; only in the case of the hyena, among the carnivores, is a true hemochoria1 situation found. Here the resemblance to the placenta of the New World monkeys is striking. Evolutionary considerations. The hemochorial placenta is found in a variety of unrelated animals. Labyrinthine architecture characterizes the placenta of some insectivores, lagomorphs, most rodents, many Chiroptera, the hyracoids, and sirenians.l” The hemochorial villous state is found in the insectivora (Tenrecidae) ,I0 among all three suborders of the Anthropoidea,‘, lo, ” among the edentates (Dasypodidae and Myrmecophagidae) , 8 and among the rodents in the Anomaluroidea.6 Principles of parallel evolution must be operative, for it seems highIy unhkeIy that phylogenetic reiationships can be established among all animals with hemochorial placentas. Although the recent exceptions to the interordinal relationships postulated in Mossman’s stimulating
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Am. J. Obst. L Gynec.
monograph fail to detract from its genera1 value, the occurrence of the hemochorial placenta in some of the more primitive and less specialized mammals casts serious doubt on the validity of the Grosser concept, supported by Hill,l” of the modern epitheliochorial placenta as the ancestral type. Evidence supports instead the theories of Wislockizl and Mossma.n,l” that relegate the endotheliochorial and hemochorial labyrinths to primitive status. It is interesting that, except for the anthropoids and insectivores, most of the animals with hemochorial villous placentas occupy rather isolated taxonomic positions. According to Simpson,Z” the Hyaenidae, much the smallest family of carnivores, are a late (Miocene) offshoot of the viverrids, representing a somewhat aberrant group. The nine-banded armadillo, too, occupies a rather isolated position in the Dasypodini among the Dasypodoidea. Mossman,l” in fact, regards their fetal membranes as the most aberrant of any mammalian group because of their polyembryony, their hemochorial villous placenta resembling that of the anthropoids, the early and complete inversion of the yolk as in the higher Rodentia, and the MC, orientation of the disc and first attachment to the uterus just the opposite of that in the rodents. With regard to the classification of the Anomaluroidea, Simpson’6 places them with the sciuromorphs, fautp dc micux, considering them “the most dubious members of the dubious order.” -4ttempts to establish evolutionary relationships according to the presence and variety of hemochorial placenta are further thwarted by the striking resemblance of the mid-gestational and full-term placenta of thr hyena to the mature placenta of the New World monkeys. A generalization that appears more plausible on the basis of the descriptions here set forth is that the hemochorial condition, having probably arisen independentIy in severa unreIated mammalian groups, results in each case from extensive erosion of maternal vessels associated with suppression of maternal capillary growth; the labyrinthine and villous condi-
V&me Number
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hemochorial
tions, furthermore, are not fundamentally different, the breakdown of syncytial connections converting the former to the latter, and the lamellae to villi. Circulatory relationships. When Mossmanl” described the opposing directions of flow of the fetal and maternal blood in the labyrinth of the rabbit, he established a principle of countercurrent flow in the placenta, whereby reduced fetal blood first contacts venous and then increasingly arterialized maternal blood. Basic agreement followed in recognizing the principle in both hemoand endotheliochorial labyrinths, but in the case of the hemochorial villous placentas, such as those of the anthropoids, there was no such unanimity. Ramsey141 I5 has summarized the thinking that preceded her elucidation of the physiological theory of the human placental circulation. Bumm’* 24 wrote that maternal blood entered the intervillous space near the summits of maternal septa and that the venous return was entirely basal. SpanneP denied the random distribution of arteries and veins, stating that the venous return from the placenta was exclusively marginal. Stieve17 disagreed with both Bumm and Spanner, suggesting that all primate placentas, including that of man, were basically labyrinthine, comprising an intercommunicating network formed by the fusion of villous tips, with fetal vessels running uninterruptedly from one villus to another. Kline*l later showed that the apparent intervillous connections were, in fact, results of the organization of minute hematomas caused by the occlusion of fetal blood vessels, and that direct vascular connections were nonexistent. In comparing the circulation of the maternal blood in the mature placenta of the platyrrhine monkey with that in the typical labyrinth, HilP noted a very close similarity in the entry of arterial blood through septa and the exit through the base. Ramsey extended the analogy to include the villous placenta, regarding the amorphous blood lake as a substitute for closed maternal capillary channels. She suggested that the separation of the afferent and
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767
eff erent bloodstreams was accomplished by pressure differentials rather than by morphologic factors. In the villous hemochorial placentas of both the armadillo and the hyena, considerable improvement in the mechanics of countercurrent flow is achieved, albeit by rather different vascular adaptations. In the armadillo invasion of the maternal blood sinuses with subsequent enlargement by the villi to form the intervillous space is the unique feature of placentation, according to Enders.* The maternal vascular system in Dasypus is uninterrupted except at the fundus and the consequent blood flow is unidirectional. Since the maternal blood &ters the sinuses under the endometrial arches, thence flowing toward the muscular layer, relatively less mixing of oxygenated and reduced blood occurs than in the intervillous spaces of man and Old World monkeys, in which blood both enters and leaves through the basal plate. The fetal blood vessels, too, enter the intervillous space near the luminal border of the placenta and the venous return is from the muscular wall toward the lumen. The result is a rough countercurrent, with more highly oxygenated fetal blood near the surface. Enders makes the significant qualification, in the case of the armadillo, that direct countercurrent flow is precluded by the random distribution of the highly branched and anastomotic villi, which form a rather complicated spongework. In the the direction of fetal capillaries, therefore, blood flow bears no fixed relationship to that of the maternal flow. In the case of the spotted hyena it is significant that the maternal arterial blood is discharged not at the basal plate into the intervillous space, as in man and the macaque, but high in the fetal portion of the placenta at or near the summits of complete maternal septa, and that the venous blood is returned to the uterine veins solely at the placental base, as in the case of the New World monkeys and most carnivores, which possess labyrinthine placentas. The placental circulation in Crocuta thus resembles closely the human model proposed by Bumm, while
768 Wynn
differing greatly from what has since been learned of the human circulation through Ramsey’s research. Although Enders’ comments regarding Dasypus are somewhat applicable to Crocuta as well, the complete septa and the less randomly oriented terminal villi of the hyena create the closest approximation to ideal countercurrent flow that has been demonstrated in any villous placenta thus far examined. Summary
and
conclusions
1. Hemochorial villous placentas of man. Old World and New World monkeys, the armadillo and the scaly-tailed squirrel are histologically described and compared. 2. Modes of origin of the hemochorial condition in the various mammalian Orders and the transitional stagesfrom labyrinthine to villous placentas are described. 3. Direct phylogenetic relationships among the diverse mammals with hemochorial placentas are denied. 4. The histological “barrier” varies among
villous hemochorial placental types, Absence of Langhans cells in the armadillo and “intraepithelial” capillaries in the hyena minimize the thickness of the histological barrier in the respective species. 5. Vascular adaptations likewise vary, with approximate, and almost ideal, countercurrent flow found in Dasypus and Crocuta, respectively. 6. Morphologic variants among hemochorial placentas suggestcaution in the intergeneric extrapolation of physiologic data.
Dr. .4llen (:. Enders,Departnrent of Anatomy, Washington.University School of Medicine, St. Louis, Missouri, generouslysupplieda sectionof the placenta of Dasypusnovemcinctus.Professor E. C. Amoroso, Department of Physiology, Royal Veterinary Collrgc, IJniversity of London, not only provided the photomicrographs of placenta of Anomalurus, but made available the author the facilities of his department, which the study of Crocufn crocuta was formed.
the to in per-
REFERENCES
1. Amoroso, E. C.: In Parkes, A. S., editor: Marshall’s Physiology of Reproduction, London, 1952, Longmans, Green & Co., Inc., vol. ‘) p. 127. 2. &~oroso, E. C.: In Flexner, L. C., editor: Gestation, Tr. of the First Conference, New York, 1954, Josiah Macy, Jr. Foundation, p. 1’19. 3. Amoroso, E. C.: In Villee, C. A., editor: Gestation, Tr. of the Fifth Conference, New York, 1958, Josiah Macy, Jr. Foundation, p. 15. -4. Amoroso, E. C.: Ann. New York Acad. SC. 75: 855, 1959. 5. Amoroso, E. C.: Brit. M. Bull. 17: 1, 1961. 6. Branca, A.. and Cretin, A.: Compt.-rend. Assoc.anat. 20: 139, 1925. 7. Bumm, E.: Arch. GynHk. 43: 181, 1893. 8. Enders, A. C.: J. Anat. 94: 34, 1960. 9. Hamilton, W. J., and Boyd, J. D.: J. Anat. 94: 297, 1960. 10 Hill, J. P.: Phil. Tr. Roy. Sot. London, Series B. 221: 45. 1932. 11. Kline, B. S.: A&. 5. OBST. & GYNEC. 61: 1065,- 1951. H. W.: Am. J. Anat. 37: 433, 1926. 12. Mossman,
13. 14. 15. 16. 17. 18. 19. 20. 21. ‘,‘J *-. ‘3. 24 25.
Mossman, H. W.: Contrib. Embryol. 26: 129. 1937. Ramsey, E. M.: Ann. New York Acad. SC. 75: 726, 1959. Ramsey, E. M.: Au. J. OBST. & GYNEC. 84: 1649. 1962. Simpson, G. G.: Bull. Am. Mus. Nat. Hist. 85: 1, 194.5. Stieve, H.: Zentralbl. Gynak. 65: 370, 1941. Spanner, R.: Ztschr. Anat. 105: 163, 1935. Wimsatt, W. A.: .4&r. J. OBST. & Guxec. 84: 1568, 1962. Wislocki, G. B.: Anat. Rec. 52: 381, 1932. Wislocki, G. B.: Contrib. Embrvol. 20: 51. 1929. Wislocki, G. B.. and Dempsey, E. W.: Am. J. Anat. 78: 1. 1946. Wislocki, G. B., and Streeter, G. I,.: Gontrib. Embryo]. 27: 1, 1938. Wynn, R. M.: AM. J. OBST. & GYNEC. 87: 829, 1963. Wynn, R. M., and Amoroso, E. C:.: .4m. J. Anat. (In press.) 450 Clarkson Avenue Brooklvn 3. New York