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. 2010 Jan 7;216(3):292–300. doi: 10.1111/j.1469-7580.2009.01184.x

Maternal and fetal microvasculature in sheep placenta at several stages of gestation

Shireen A Hafez 1, Pawel Borowicz 2, Lawrence P Reynolds 2, Dale A Redmer 2
PMCID: PMC2829387  PMID: 20070427

Abstract

Maternal and fetal microvasculature was studied in ewes at days 50, 90 and 130 of gestation using microvascular corrosion casting and scanning electron microscopy. Microvascular corrosion casts of caruncles at day 50 were cup-shaped with a centrally located cavity. Branches of radial arteries entered the caruncle from its base and ramified on the maternal surface of the caruncle. Stem arteries broke into an extensive mesh of capillaries forming crypts on the fetal surface. The architecture of the caruncle at day 90 was similar to what was found at day 50 but the vascularity and the depth of the crypts increased in correspondence to increased branching of fetal villi. The substance of the caruncle was thicker at day 130 compared with day 50, with no remarkable difference compared with day 90. Capillary sinusoids of irregular form and diameter were observed on the fetal surface of the caruncle at all stages. These sinusoids may reduce blood flow resistance and subsequently increase transplacental exchange capacity. A microvascular corrosion cast of the cotyledon was cup-shaped with wide and narrow sides. Cotyledonary vessels entered and left the cotyledon from the narrow side. A cotyledonary artery gave proximal collateral branches immediately after entering the cotyledon and then further branched to supply the remaining portion of the cotyledon. Vessel branches broke into a mesh of capillaries forming the fetal vascular villi. Fetal villi that were nearest to the center of the cotyledon were the longest. Capillaries forming villi were in the form of a web-like mesh, were irregular in size and had sinusoidal dilations. The architecture of the cotyledon at day 90 was similar to day 50, but the vascularity increased. Branching of the fetal villi became more abundant. This extensive branching presumably allows a higher degree of invasion and surface contact to maternal tissues. At day 130, the distal portions of the fetal villi showed low ridges and troughs to increase the surface area for diffusion. Branching of fetal villi appears to influence the elaboration of maternal crypts in all stages of gestation. However, correspondence between crypts and villi is restricted to distal portions of fetal villi.

Keywords: fetal vascular system, maternal vascular system, microvascular corrosion casting, sheep placenta

Introduction

The sheep placenta is chorioallantoic, adeciduate, cotyledonary and villous type (Kaufmann & Burton, 1994; Leiser & Kaufmann, 1994). The interhemal barrier is classified as synepitheliochorial (Wooding, 1992; Leiser & Kaufmann, 1994) because of the fusion of the binucleate trophoblasts with the uterine epithelium. The efficiency of materno-fetal exchange might be affected in part by the interhemal distance of the sheep placenta, and the epitheliochorial placentas may be considered as less efficient at the transfer than those with a shorter interhemal distance. The idea of considering the epitheliochorial placenta as less efficient may not be accurate because several other factors, i.e. the species-specific degree of permeability of the various layers making up the materno-fetal barrier, the actual thickness of these layers, and the fetal and maternal vascular systems arrangement, may be very important in determining the efficiency of transplacental exchange.

The maternal and fetal vascular systems arrangement may exhibit a concurrent, counter-current, cross-current or multivillous pattern (Kaufmann & Burton, 1994). Concurrent flow is the least efficient pattern and is not seen in the placentas of mammals. The counter-current arrangement, however, is the most efficient arrangement. The maternal and fetal vascular systems in sheep and goats have been examined by some investigators, although they are few because of the complexity of these systems and the difficulty associated with such studies. Barcroft & Barron (1946) showed a counter-current flow in the ovine placenta. Steven (1966) showed a cross-current flow in the ovine placenta. Makowski (1968) showed a cross-current arrangement in the ovine and caprine placentas but based on a different anatomical arrangement from that shown by Steven (1966). One reason for these controversial results was the methods used, which differed among authors. Barcroft & Barron (1946) used reconstructed histological serial sections and corrosion casts observed under a dissecting scope. Makowski (1968) used conventional India ink- and latex-injected specimens. Steven (1966) employed India ink- and latex-injected specimens and corrosion casts observed under a dissecting scope. Although these studies yielded much information, they suffered from inherent limitations, such as a lack of three-dimensionality and limited resolution of fine details. The potential for misinterpretation is high. Prior to our study on the goat placenta (Hafez et al. 2007a), microvascular corrosion casting combined with observation by scanning electron microscopy had been used to study the uterine vasculature in the goat only once (Leiser, 1987). Leiser (1987) examined the principle of blood flow in the caprine placenta using microvascular corrosion preparations of both maternal and fetal vessels, and concluded that a combination of a counter-current and cross-current arrangement is present. We (Hafez et al. 2007a) showed an overall multivillous arrangement in the goat placenta.

Microvascular corrosion casts appeared to be the most efficient way of studying these extremely complex systems. They provide a three-dimensional replica of the maternal and fetal vascular systems and can be compared more or less with the previous work. Furthermore, although the placenta has been studied to a certain extent, none of the authors mentioned above provided the developmental features of the uterine and fetal vascular systems with advancing gestation.

The importance of vascular development to placental function has long been recognized (Stegeman, 1974; Reynolds & Redmer, 2001; Reynolds et al. 2005a,b;) because it affects fetal growth and subsequent health and life-long productivity (Barker & Clark, 1997; Trahair et al. 1997; Greenwood et al. 1998, 2000; Breier et al. 2001; Oken & Gillman, 2003; Reynolds et al. 2005b). The placenta is one of the most important transient organs and it has been the subject of extensive research. The study of placental vascular growth in sheep is valuable and necessary because of the ease of sheep as a model for studying placental function (Reynolds et al. 2005b; Borowicz et al. 2008) and the presence of large body of literature on the subject. The question is what is the structure and arrangement of the maternal and fetal vascular systems in sheep, and how does it compare with the systems reported in the goat? What impact would this arrangement have on the physiological efficiency of the placenta? In the present study we studied the three-dimensional architecture of the maternal and fetal vascular systems in sheep and its developmental features with advancing gestation.

Materials and methods

All procedures used in this work were approved by the North Dakota State University Animal Care and Use Committee. We examined sheep placenta at day 50 (n = 4), day 90 (n = 7) and day 130 (n = 4) of gestation. The ewes that were examined at day 90 and day 130 had twin fetuses. Two animals at day 50 had one fetus and two had triplets. The ewes were stunned and exsanguinated and their reproductive tracts were exteriorized. Prior to stunning, ewes were intravenously administered 10 mL heparin (1000 IU). In the case of uteri having two or more fetuses, one horn was used for making vascular casts of the maternal portion of placentomes (caruncles) and the other was used for making casts of the fetal portion of placentomes (cotyledons). In the case of a singleton pregnancy, the gravid horn was used for both; a portion was clamped and used for making vascular casts of cotyledons, whereas the remaining portion was used for making vascular casts of caruncles.

For maternal vascular system injection in three to four representative placentomes, a branch off the arcuate artery near the ovary (for nomenclature of the uterine vessels see Hafez et al. 2007b), which supplies the caudal area of the uterine body, and the uterine branch of the vaginal artery were cannulated. Both branches were infused with heparinized physiologic saline (40 °C) mixed with procaine (0.5 mg mL−1). A vein draining the vasculature was opened as an outflow port. For fetal vascular system injection, a branch of the umbilical artery was cannulated and perfused as described for the caruncles (above). A branch of the umbilical vein was opened as an outflow port. Following saline perfusion, tissues were perfused with modified Batson's No. 17® mixture (Polysciences, Inc., Warrington, PA, USA). For details about microvascular corrosion casting and preparation of the Batson's mixture, see Hafez et al. (2007a). After perfusion was complete, the tract was kept immersed in saline at room temperature (25 °C) overnight. Each specimen was then left in distilled water for 3 days at 40 °C and then immersed in distilled water mixed with papain (2.0 g L−1, 40 °C) (Adolph's Tenderizer, available from local food suppliers) for 2–3 days. Corrosion was performed by alternating immersion in 40% KOH (Fisher Scientific International Inc.) and distilled water at 40 °C. After the completion of maceration, caruncular and cotyledonary casts were stored dry under vacuum after immersion in 95% ethanol for 15 min. Casts were mounted on aluminum stubs and sputter coated with a layer of palladium/gold using a Balzers SCD 030 sputter coater (BAL-TEC RMC, Tucson, AZ, USA). Images were obtained using a JSM-6300 scanning electron microscope (JOEL, USA, Peabody, MA, USA) using an accelerating voltage of 15 keV. Some caruncles and cotyledons were studied intact and some were manually sectioned.

Results

Architecture at day 50

Caruncles

Microvascular corrosion casts of caruncles were cup-shaped with a centrally located cavity on the fetal side. Maternal vessels entered the caruncle from its base (convex maternal surface). Caruncles were supplied by branches of radial arteries. These branches pursued a tortuous course and ramified on the maternal surface of the caruncle (Fig. 1). Branches of radial arteries supplying caruncles bent and followed the convex contour of the maternal surface (Fig. 2). Stem arteries were derived from branches of radial arteries along the convexity of the maternal surface. They branched through the substance of the caruncle toward the fetal surface. In their course from the maternal to the fetal surface they tended to run radially parallel to each other and branched in a narrow angle (Fig. 3). This pattern of branching gave the striped gross appearance of the sectioned caruncle. These vessels broke into an extensive mesh of capillaries on the fetal surface, which arranged in the form of crypts (Figs 4 and 5) serving to receive the fetal villi. A group of capillaries coalesced to form a capillary sinusoid. Capillary sinusoids were observed on the caruncle near the fetal surface (Fig. 4). Sinusoids were irregular in form and diameter.

Fig. 1.

Fig. 1

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A photographic image of a microvascular corrosion cast of a caruncle from a pregnant ewe at day 50 that has been coated with gold/palladium. Branches and tributaries of radial vessels (BRV) pursue a tortuous course to and from the base of the caruncle and ramify on its maternal surface (shown surface). Scale bar = 3 mm.

Fig. 2.

Fig. 2

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Scanning electron micrograph of a microvascular corrosion cast of a caruncle from a pregnant ewe at day 50 showing that branches of radial arteries (BRA) bend and follow the convex contour of the maternal surface, where they give rise to stem arteries. Scale bar = 1 mm.

Fig. 3.

Fig. 3

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Scanning electron micrograph of a microvascular corrosion cast of a caruncle from a pregnant ewe at day 50 showing the angle of branching of stem arteries. They tend to run parallel to each other and branch in a narrow angle (arrows). Scale bar = 100 μm.

Fig. 4.

Fig. 4

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Scanning electron micrograph of a microvascular corrosion cast of a caruncle from a pregnant ewe at day 50 viewed from the fetal side, displaying maternal crypts (CR). CS, capillary sinusoid. Scale bar = 100 μm.

Fig. 5.

Fig. 5

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Scanning electron micrograph of a microvascular corrosion cast of a sectioned caruncle from a pregnant ewe at day 50 viewed from an angle perpendicular to the longitudinal axis of the caruncle displaying maternal crypts (CR). Scale bar = 100 μm.

Capillary meshes could lead back to the maternal side of the caruncle through venules, small veins and large vein, consecutively. Veins ran in a similar manner and in the opposite direction to that of arteries. They distributed on the maternal surface as arteries (Fig. 1). Veins and arteries could be distinguished from each other by the impression patterns of endothelial cells and nuclei on their surfaces (Fig. 6). In arteries, impressions of the endothelial cells were deep, slender and regularly arranged parallel to the longitudinal axis of the vessel (Fig. 6A). In veins, they were shallow, more round and randomly oriented (Fig. 6B).

Fig. 6.

Fig. 6

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Scanning electron micrograph of a microvascular corrosion cast of an artery (A) and vein (B). Note the impression patterns made by the endothelial cell borders and nuclei. On an artery (a in A), they are deep, slender and arranged parallel to the longitudinal axis of the vessel. On a vein (v in B), they are shallow, more round and randomly oriented. Scale bar = 10 μm in A and 100 μm in B.

Cotyledon

The microvascular corrosion cast of the cotyledon was cup-shaped with wide and narrow sides. Cotyledonary vessels entered and left the cotyledon from the narrow side (Fig. 7). Usually, a single artery and a single vein supplied and drained, respectively, the cotyledon. A cotyledonary artery penetrated through the substance of the cotyledon at different levels. Proximal collateral branches were given off immediately after entering the cotyledon to supply the proximal parts of the cotyledon. Further branching occurred afterward to supply the middle portions. Distally the artery terminated to supply the distal parts of the cotyledon. Vessel branches broke into a mesh of capillaries, which arranged to form fetal vascular villi in the cotyledon near the maternal surface (Figs 7 and 8A). These fetal villi formed most of the substance of the cotyledon. The fetal villi that were nearest to the center of the cotyledon were the longest. The fetal villi closest to the periphery tended to be shorter.

Fig. 7.

Fig. 7

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Scanning electron micrograph of a microvascular corrosion cast of a sectioned cotyledon from a pregnant ewe at day 50 showing cotyledonary vessels (CV) entering the cotyledon from its narrow end. BCV, branches of cotyledonary vessels; FV, fetal villi. Spaces (S) between villi are for interdigitation with maternal tissues. Scale bar = 1 mm.

Fig. 8.

Fig. 8

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Scanning electron micrograph of a microvascular corrosion cast of a cotyledon from a pregnant ewe at day 50 viewed from the maternal side displaying fetal villi (FV) (A). Spaces (S) between villi are for interdigitation with maternal tissues. (B) Capillary sinusoids (CS) on the fetal villi. Scale bar = 100 μm.

Capillaries forming villi were in the form of a web-like mesh, were irregular in size and had sinusoidal dilations (Fig. 8B). Capillaries united to form venules, which in turn formed small veins and large veins and exited the cotyledon from its narrow end (Fig. 7).

Architecture at day 90

Caruncles

The architecture of the caruncle was similar to day 50 but the thickness of the substance of the caruncle increased due to increased vascularity compared with day 50. The depth of the crypts seemed to increase in correspondence with increased branching of fetal villi (see below) (Fig. 9). Capillary sinusoids were also evident at this stage (Fig. 9). These structures, which are surprisingly large for sinusoids, may alternatively represent leakage of the casting medium into the hemophagous zone, which occurs in the central depression of the placentome where extravasated maternal blood collects between the maternal and fetal components, and maternal erthyrocytes are phagocytosed by the trophoblast for the transport of iron.

Fig. 9.

Fig. 9

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Scanning electron micrograph of a microvascular corrosion cast of a caruncle from a pregnant ewe at day 90 viewed from the fetal side. Note the presence of deep crypts (CR) and capillary sinusoids (CS). Scale bar = 100 μm.

Cotyledon

The architecture was similar to day 50 but the size of the cotyledon increased due to increased vascularity. Branching of the cotyledonary vessels increased before breaking into capillary meshes (Fig. 10). Branching of the fetal villi became more abundant (Fig. 11). This extensive branching presumably allows a higher degree of invasion and surface contact to maternal tissues. On longitudinal section, the depth of the spaces where maternal tissues interdigitated with fetal tissues could be appreciated (Fig. 12), which gave an indication of the great extent of invasion of fetal tissues to maternal tissues.

Fig. 10.

Fig. 10

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Scanning electron micrograph of a microvascular corrosion cast of a sectioned cotyledon from a pregnant ewe at day 90. Note the increased branching of cotyledonary vessels (CV). Scale bar = 1 mm.

Fig. 11.

Fig. 11

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Scanning electron micrograph of a microvascular corrosion cast of a cotyledon from a pregnant ewe at day 90 viewed from the maternal side showing extensive branching of fetal villi. The entire image is filled with fetal villi. Scale bar = 100 μm.

Fig. 12.

Fig. 12

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Scanning electron micrograph of a microvascular corrosion cast of a sectioned cotyledon from a pregnant ewe at day 90 displaying the depth of the spaces (S) where the maternal tissues interdigitate with the fetal tissues. Scale bar = 100 μm.

Architecture at day 130

Caruncle

No major changes were observed in the architecture of the caruncle compared with day 90. The architecture of the vasculature was similar to day 50. However, the substance of the caruncle was thicker at day 130 compared with day 50, with no remarkable difference compared with day 90. Crypts were deeper and had more compartments, which corresponded to more extensive branching of fetal villi (Fig. 13).

Fig. 13.

Fig. 13

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Scanning electron micrograph of a microvascular corrosion cast of a sectioned caruncle from a pregnant ewe at day 130 displaying the depth of the crypts (CR). The fetal surface of the caruncle is at the lower right hand corner. Scale bar = 1 mm.

Cotyledon

At this stage, in addition to increased branching of fetal villi, the distal portions of the fetal villi showed low ridges and troughs to increase the surface area for diffusion (Fig. 14).

Fig. 14.

Fig. 14

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Scanning electron micrograph of a microvascular corrosion cast of a cotyledon from a pregnant ewe at day 130 viewed from the maternal side displaying ridges (Rd) and troughs (Tr) on the distal portions of fetal villi. Scale bar = 100 μm.

Discussion

Microvascular corrosion casting provided a three-dimensional picture of the architecture of the maternal (caruncular) and fetal (cotyledonary) vascular systems. Fetal villi interdigitate with maternal crypts. Maternal crypts are cavities (Figs 4, 5, 9 and 13) that are best seen from the fetal surface of the caruncle. There are also spaces (Figs 7, 8 and 12) present in the cotyledon where maternal tissues interdigitate with fetal tissues. These spaces are found in between fetal villi. Both maternal and fetal components of the placentome have spaces or cavities for the other component. The tissues between those spaces are like fingers, which could be seen when separating a caruncle from a cotyledon. This arrangement of cavities or spaces in between the villi increases the surface area available for the diffusion of nutrients, gases and wastes between the maternal and fetal portions of the placentome.

The branching of fetal villi appears to influence the elaboration of maternal crypts at all stages of gestation; however, crypts do not appear to have the same extensive pattern of branching of the fetal villi. In other words, not every area on the fetal villi contacts an area on the maternal crypts. This may decrease the surface area available for diffusion and slow the process of transplacental exchange. The latter might be beneficial and might counteract the negative effect of the earlier. Extensive branching might be a product of the site-specific production of growth factors in fetal tissues or maternal tissues (Hafez et al., unpublished data). Indeed, an array of angiogenic growth factors from ovine placentomes has been reported (Redmer et al. 2005).

Fetal villi appear to be longer than the corresponding crypts because the proximal folding pattern of the fetal villi does not appear to follow that of the maternal crypts. Correspondence between crypts and villi is restricted to distal portions of fetal villi. Fetal villi pass through the spaces in between the maternal capillary sinusoids present on the fetal surface of the caruncle. Maternal capillary sinusoids contact the proximal intervillous portions between the bases of the fetal villi and the proximal portions of the core of the villi. A gap appears between the fetal surface level of maternal crypts and capillary sinusoids. The length of this gap and the distance that the villi travel to the surface level of capillary sinusoids account for the increase in length of fetal villi compared with their corresponding crypts. Spaces between maternal capillary sinusoids allow for the passage of the proximal cores of fetal villi, which further branch after passing the level of maternal sinusoids to interdigitate with their corresponding crypts.

The previous arrangement is true more in the center than at the periphery. Divided crypts could be seen at the periphery, which correspond to short and fairly low-branched fetal villi. Non-divided crypts seen in the center correspond to long fetal villi, which branch deeper in the substance of the caruncle. These morphological observations should be considered when studying the development of the vasculature. These centrally located crypts may be considered as less elaborate crypts, whereas in fact they may be more elaborate and correspond to more extensive branched fetal villi.

We demonstrated, for the first time, the presence of capillary sinusoids on the fetal surface of the caruncle in goats (Hafez et al. 2007a). These sinusoids were also seen in sheep in the present study. Borowicz et al. (2003) demonstrated the presence of large capillaries in the maternal caruncular tissues. Because of the inherent limitation in visualizing the vasculature using conventional histological sections, the nature of these capillaries was not identified. In both our previous study and the present study, using microvascular corrosion casting coupled with scanning electron microscopy, we illustrated the nature of these large capillaries, which are capillary sinusoids. The presence of capillary sinusoids may reduce the blood flow resistance and subsequently increase the transplacental exchange capacity. This significance agrees with the functional observation reported by Vonnhame et al. (2004a,b); and Reynolds et al. (2005b). Vonnhame et al. (2004a,b); reported that the resistance across the cotyledonary microvascular bed in an in-vitro perfusion system is two-fold greater than that of the caruncular microvascular bed at physiological flow rates throughout the last half of gestation. The increase in surface area for diffusion presented by the presence of capillary sinusoids and crypts should also be met by increased surface area for absorption in the fetal side through increased branching of the fetal villi with advancing gestation. Generally larger vessels are demonstrated more in caruncles than in cotyledons. Cotyledonary arteries divide soon after entering the cotyledon and its branches soon break into an extensive capillary bed.

Fetal villi are arranged in such a way to interdigitate with crypts. Accounting for the direction of blood flow to the fetal and maternal tissues gives a counter-current arrangement in these areas of interdigitation. However, in some areas of the distal portions of the fetal villi and crypts, vessels may have the same direction of blood flow on both maternal and fetal sides; this pattern yields a concurrent blood flow. At the level of the fetal surface of the caruncle, fetal villi may cross maternal capillary sinusoids; this arrangement yields a cross-current flow. The combination of concurrent, cross-current and counter-current flow gives an overall multivillous type flow. The efficiency of transplacental exchange given by this type of flow correlates well with the neonate : placental weight ratio reported in sheep, which is 10 : 1 (Leiser, 1987).

The most striking expansion of the placentomal vasculature occurs early during pregnancy in both maternal and fetal tissues. This is in agreement with the fact that most of the placental growth occurs during the first half of gestation (Reynolds et al. 2005a,b;) and indicates that most of the placental growth that occurs early during pregnancy is due to vascular growth. At later stages of pregnancy, expansion of the placentomal vasculature is less relative to early pregnancy. This expansion is more striking in the fetal tissues compared with maternal tissues. It seems that branching of fetal villi compensates for limitation in size; in other words, increasing the surface area for diffusion to keep up with the increasing fetal demand. This observation is supported by what was reported by Borowicz et al. (2007) in sheep during the last half of pregnancy, i.e. the increasing metabolic demands of fetal growth appear to be met to a large extent by branching of the fetal villi. It was also supported by observations reported in sheep by Stegeman (1974), in humans by Kaufmann et al. (2004) and in cattle by Reynolds & Redmer (1995).

Regardless of the relative growth of placental tissues, functionally, under normal circumstances, the placenta has to meet the increasing fetal requirement throughout gestation. During the later stages of gestation, the fetal requirement increases (Reynolds et al. 2005a) but there is no apparent corresponding modification in vascular morphology, which draws our attention to what happens physiologically in blood flow to placental tissues and the size/volume of the vascular bed. Uterine and umbilical blood flow increases continuously during gestation to meet fetal demands (Reynolds et al. 2005a). Other placental functions, such as transport of oxygen and water and uptake of glucose, also increase exponentially as gestation advances (Reynolds et al. 2005a).

The general architecture of the goat (Hafez et al. 2007a) and sheep (present study) caruncle is similar. However, because of the difference in shape of the placentome, salient differences should be noted. Because of the great convexity of the maternal surface of the sheep caruncles, branches of radial arteries bend to follow the contour of the maternal surface and then give rise to stem arteries along the convexity. Stem arteries are given from all levels in the case of the goat placentome. The branching pattern of stem arteries within the substance of the caruncle to the level of the fetal surface is similar in these two species. In the goat, capillary sinusoids cover more or less the entire fetal surface of the caruncle and can easily be seen when examining the fetal surface. In the case of sheep, the fetal surface of the caruncle is greatly convex and it is difficult to appreciate the extent of capillary sinusoids on the surface.

Some similarities between the human and ruminant placenta have been noted (Leiser et al. 1997). The architecture of the fetal vascular trees is similar, which implies that the fetal vascular tree may be a workable model for the human. The presence of capillary sinusoids on the surface of fetal villi adds to this similarity. These sinusoids are also present in the fetal side of human placenta.

Acknowledgments

This work was supported in part by Hatch Project ND01727 of the North Dakota Agricultural Experiment Station and NIH grant HD045784.

References

  1. Barcroft J, Barron DH. Observation upon the form and relations of the maternal and fetal vessels in the placenta of the sheep. Anat Rec. 1946;94:569–595. doi: 10.1002/ar.1090940403. [DOI] [PubMed] [Google Scholar]
  2. Barker DJ, Clark PM. Fetal undernutrition and disease in later life. Rev Reprod. 1997;2:105–112. doi: 10.1530/ror.0.0020105. [DOI] [PubMed] [Google Scholar]
  3. Borowicz PP, Arnold DR, Grazul-Bilaska AT, et al. Modeling vascular growth in the sheep placentome. Biol Reprod. 2003;68(Suppl. 1):150. [Google Scholar]
  4. Borowicz PP, Arnold DR, Johnson ML, et al. Placental growth throughout the last two-thirds of pregnancy in sheep: vascular development and angiogenic factor expression. Biol Reprod. 2007;76:259–267. doi: 10.1095/biolreprod.106.054684. [DOI] [PubMed] [Google Scholar]
  5. Borowicz PP, Hafez SA, Redmer DA, et al. Chapter 10. Methods for evaluating uteroplacental angiogenesis and their application using animal models. In: Cheresh D, editor. Methods in Enzymology, Vol. 445, Angiogenesis, In Vivo, Part B. NY: Elsevier; 2008. pp. 229–253. [DOI] [PubMed] [Google Scholar]
  6. Breier BH, Vickers MH, Ikenasio BA, et al. Fetal programming of appetite and obesity. Mol Cell Endocrinol. 2001;20:73–79. doi: 10.1016/s0303-7207(01)00634-7. [DOI] [PubMed] [Google Scholar]
  7. Greenwood PL, Hunt AS, Hermanson JW, et al. Effects of birth weight and postnatal nutrition on neonatal sheep. I. Body growth and composition, and some aspects of energetic efficiency. J Anim Sci. 1998;76:2354–2367. doi: 10.2527/1998.7692354x. [DOI] [PubMed] [Google Scholar]
  8. Greenwood PL, Slepetis RM, Bell AW. Influences on fetal and placental weights during mid to late gestation in prolific ewes well nourished throughout pregnancy. Reprod Fertil Dev. 2000;12:149–156. doi: 10.1071/rd00053. [DOI] [PubMed] [Google Scholar]
  9. Hafez SA, Caceci T, Freeman LE, et al. Angiogenesis in the caprine caruncles in non-pregnant and pregnant normal and swainsonine-treated does. Anat Rec. 2007a;290:761–769. doi: 10.1002/ar.20548. [DOI] [PubMed] [Google Scholar]
  10. Hafez SA, Freeman LE, Caceci T, et al. Study of the vasculature of the caprine reproductive organs using the tissue-clearing technique, with special reference to the angioarchitecture of the utero-ovarian vessels and the adaptation of the ovarian and/or vaginal arteries to multiple pregnancies. Anat Rec. 2007b;290:389–405. doi: 10.1002/ar.20496. [DOI] [PubMed] [Google Scholar]
  11. Kaufmann P, Burton G. Anatomy and genesis of the placenta. In: Knobil E, Neill JD, editors. The Physiology of Reproduction. New York: Raven Press Ltd; 1994. pp. 441–484. [Google Scholar]
  12. Kaufmann P, Mayhew T, Charnock-Jones DS. Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta. 2004;25:114–126. doi: 10.1016/j.placenta.2003.10.009. [DOI] [PubMed] [Google Scholar]
  13. Leiser R. Mikrovasckularisation der ziegenplazenta, dargestellt mit rasterelektronisch untersuchten gefassausgussen. Schweiz Arch Tierheilkd. 1987;129:59–74. [PubMed] [Google Scholar]
  14. Leiser R, Kaufmann P. Placental structure: in a comparative aspect. Exp Clin Endocrinol. 1994;102:122–134. doi: 10.1055/s-0029-1211275. [DOI] [PubMed] [Google Scholar]
  15. Leiser R, Krebs C, Ebert B, et al. Placental vascular corrosion cast studies: a comparison between ruminants and humans. Microsc Res Tech. 1997;38:76–87. doi: 10.1002/(SICI)1097-0029(19970701/15)38:1/2<76::AID-JEMT9>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  16. Makowski EL. Maternal and fetal vascular nets in placentas of sheep and goats. Am J Obstet Gynecol. 1968;100:283–288. [Google Scholar]
  17. Oken E, Gillman MW. Fetal origins of obesity. Obes Res. 2003;11:495–506. doi: 10.1038/oby.2003.69. [DOI] [PubMed] [Google Scholar]
  18. Redmer DA, Aitken RP, Milne JS, et al. Influence of maternal nutrition on messenger RNA expression of placental angiogenic factors and their receptors at midgestation in adolescent sheep. Biol Reprod. 2005;72:1004–1009. doi: 10.1095/biolreprod.104.037234. [DOI] [PubMed] [Google Scholar]
  19. Reynolds LP, Redmer DA. Utero-placental vascular development and placental function. J Anim Sci. 1995;73:1839–1851. doi: 10.2527/1995.7361839x. [DOI] [PubMed] [Google Scholar]
  20. Reynolds LP, Redmer DA. Minireview: angiogenesis in the placenta. Biol Reprod. 2001;64:1033–1040. doi: 10.1095/biolreprod64.4.1033. [DOI] [PubMed] [Google Scholar]
  21. Reynolds LP, Borowicz PP, Vonnhame KA, et al. Animal models of placental angiogenesis. Placenta. 2005a;26:689–708. doi: 10.1016/j.placenta.2004.11.010. [DOI] [PubMed] [Google Scholar]
  22. Reynolds LP, Biondini ME, Borowicz PP, et al. Functional significance of developmental changes in placental microvascular architecture: the sheep as a model. Endothelium. 2005b;12:1–9. doi: 10.1080/10623320590933734. [DOI] [PubMed] [Google Scholar]
  23. Stegeman JH. Placental development in the sheep and its relation to fetal development. Bijdragen Tot De Dierkunde. 1974;44:3–72. [Google Scholar]
  24. Steven DH. Further observations on placental circulation in the sheep. J Physiol. 1966;183:13. [Google Scholar]
  25. Trahair JF, DeBarro TM, Robinson JS, et al. Restriction of nutrition in utero selectively inhibits gastrointestinal growth in fetal sheep. J Nutr. 1997;127:637–641. doi: 10.1093/jn/127.4.637. [DOI] [PubMed] [Google Scholar]
  26. Vonnhame KA, Ford SP, Nijland MJ, et al. Alteration in cotyledonary (COT) vascular responsiveness to angiotensin II (ANG II) in beef cows undernourished during early gestation. Biol Reprod. 2004a;70(Suppl. 1):110. [Google Scholar]
  27. Vonnhame KA, Reynolds LP, Nijland MJ, et al. Impacts of undernutrition during early to mid gestation on basal vascular tone of the cotyledonary and caruncular arterial beds in the bovine placentome. J Soc Gynecol Investig. 2004b;11(Suppl.1):222A. [Google Scholar]
  28. Wooding FBP. Current topic: the synepitheliochorial placenta of ruminants: binucleated cell fusions and hormone production. Placenta. 1992;13:101–113. doi: 10.1016/0143-4004(92)90025-o. [DOI] [PubMed] [Google Scholar]

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