The paca (Agouti paca, L) is a South American rodent that lives in forested habitats near water and feeds largely on fallen fruit. It is hunted for its meat, which is considered a delicacy, and is an important source of animal protein for rural populations. This has led to indiscriminate exploitation, resulting in a significant reduction in the population density of this species in Brazil.

We here describe the morphology of paca placenta as revealed by light microscopy and transmission electron microscopy. This study is part of a wider effort to document the reproductive physiology of paca. It is hoped that the information obtained will contribute to a rational strategy for conservation of the species and possibly for production, as paca has great potential as a commercial food animal 1.

The observations are based on placentae collected from 13 pregnant females. One was in early gestation, two in midgestation and nine near term of pregnancy. This material was collected at Paulista State University, Jaboticabal, Sao Paulo, Brazil. The research was authorized by the Brazilian Institute of the Environment and Renewable Natural Resources (IBAMA). The experimental protocol was approved by the Bioethics Committee of the School of Veterinary Medicine, University of Sao Paulo.

The animals were sedated with azaperone (Stresnil, Janssen Pharmaceutica, Brazil; 0.1 mg/kg I.M.) and given atropine (0.5 mg I.M.). Anaesthesia was induced with xylazine (Coopazine, Coopers Brazil, Sao Paulo, S.P., Brazil; 1.5 mg/kg I.M.) and ketamine (Holliday Scott S.A., Brazil; 20 mg/kg I.M.). Hemihysterectomy was then performed under aseptic conditions during inhalation anaesthesia with halothane (Hoechst, Frankfurt, Germany). Postoperatively the animals were treated with benzyl penicillin and streptomycin (Pentabiotico^®, Fort Dodge, Campinas, S.P., Brazil; 8,000–24,000 IU/kg I.M.) and an analgetic (buprenorphine, Temgesic^®, Schering-Plough, S.P., Brazil). A detailed description of the anaesthesia and surgical procedures has been published elsewhere 2.

Pieces of ten placentae were fixed in Bouin's solution or 10% formaldehyde and processed by standard histological procedures for embedding in paraplast, then sectioned at 7 μm (automatic microtome, Model RM2155, Leica, Germany). Sections were stained with haematoxylin and eosin, Masson's trichrome or Gomori's trichrome or by the periodic acid Schiff (PAS) reaction with haematoxylin as counterstain.

Seven placentae were processed for transmission electron microscopy. Small samples were fixed in 2.5% glutaraldehyede in 0.1 M phosphate buffer, pH 7.4, washed in buffer and post-fixed in 1% osmium tetroxide (Polysciences, Warrington, PA, USA). They were then dehydrated, washed with propylene oxide and embedded in Spurr's resin (Spurr's Kit, Electron Microscopy Sciences, CO, U.S.A.). 60 nm sections were made and stained with 2% uranyl acetate (5 minutes) and 0.5% lead citrate (10 minutes). The ultrastructural observations were made with a transmission electron microscope (JEOL 1010, Peabody, MA, U.S.A).

The overall plan of the paca placenta is shown schematically in Figure 1. The labyrinth is divided into lobes separated by interlobular trophoblast. Beneath this is the subplacenta, a structure unique to hystricomorph rodents. The junctional zone between these structures and the maternal decidua contains nests of giant cells. The placenta is attached to the uterus by a pedicle of maternal tissue. In addition, there is an inverted yolk sac placenta, which connects with the fetal surface of the chorioallantoic placenta.

As in other hystricomorph rodents 34, the placenta of paca consists of several lobes separated by interlobular trophoblast. The center of each lobe contains maternal arteries from which blood flows to the periphery through the trophoblastic channels of the labyrinth. In the fetal capillaries, blood flows from the periphery towards the center, allowing for countercurrent exchange 56. The interlobular regions are made up of cords of syncytiotrophoblast, which define maternal blood spaces. We show here that each interlobular region drains several lobes.

In the labyrinth, the trophoblast is bathed directly by maternal blood and is separated from the fetal capillaries by a single layer of syncytiotrophoblast. Thus the placental barrier is syncytial haemomonochorial, as in the guinea pig 789, chinchilla 10, cane rat 11, degu 12 and rock cavy 13. The apical membrane of this trophoblast, which is in contact with maternal blood, is well supplied with microvilli. There are recesses in the basal membrane and caveolae can occasionally be seen at the apical membrane. However, we did not observe transtrophoblastic channels such as those described in the degu 12.

In the interlobular region, the trophoblast contained mitochondria and rough endoplasmic reticulum. The surface in contact with maternal blood bore numerous microvilli. The interlobular trophoblast is the functional equivalent of the spongy zone of murid rodents 14. In the guinea pig it has been identified as the principal site of progesterone synthesis 15. In addition, it is thought to synthesize progesterone-binding protein 16, which is found in the plasma throughout gestation and is unique to hystricomorph rodents.

Much of the surface of the placental disk is covered by the endoderm of the parietal yolk sac. This epithelium is largely columnar and rests on Reichert's membrane. Beneath the membrane are trophoblast cells that differ from those in other regions of the placenta in their larger size, rounder form and vacuolated appearance. An appropriate designation for these cells is spongiotrophoblast. It has been shown in the guinea pig that maternal protein can cross the spongiotrophoblast and Reichert's membrane. It can then pass into the uterine lumen through the intercellular spaces between the endoderm cells, as they are not sealed by tight junctions 17. In theory the protein could then be taken up by the visceral yolk sac, but whether maternal-fetal exchange occurs by this circuitous route is open to speculation.

The subplacenta is a unique feature of hystricomorph rodents 3. Characteristic of the subplacenta of paca were the large intercellular spaces between the cytotrophoblasts and the lacunae within the syncytiotrophoblast. As in the guinea pig 18 and chinchilla 10, the lacunae in the syncytium were lined by microvilli and contained electron-dense material. It seems likely that the lacunae intercommunicate, but this requires further investigation. Wolfer and Kaufmann 19 suggested that the subplacenta might be a highly active area from a metabolic point of view. They pointed out that the structure had been carefully described, but that little was known about its function, except that it might have endocrine activity. Recently it was proposed that the subplacenta is an important source of invasive trophoblast in the guinea pig, chinchilla, capybara and degu 20.

We found multinucleated giant cells in the junctional zone between the subplacenta and decidua. Intriguingly, the cytoplasm of these cells contained electron-dense granules reminiscent of those found in the subplacental syncytium. The cytoplasm of the giant cells had areas of low electron density, a feature also shared by the subplacental syncytium. These cells were PAS-positive and may store glycogen or glycoprotein.

The placenta of paca is attached to the uterus by a prominent structure, formed largely of maternal tissue, that we have denoted the placental pedicle. It was first described by Strahl 21 and named by him the mesoplacenta. A similar structure occurs in the agouti 4, chinchilla 22 and nutria 5. The equivalent formation in the capybara and guinea pig placenta is the placental stalk 23. Trophoblast is found in the walls of the maternal vessels that pass through the pedicle to supply the placenta 4.

Like other hystricomorph rodents, paca has an inverted yolk sac placenta that persists until term. This visceral yolk sac displays folds and complex villi. The numerous digitiform projections are sometimes branched. They consist of a mesenchymal axis covered by a simple columnar epithelium of endodermal cells. The cells seem to have a high level of endocytotic activity. Similar characteristics are found in the yolk sac endoderm of the guinea pig 24, chinchilla 10 and rock cavy 13. In the guinea pig it has been shown experimentally that immunoglobulin G is taken up from the uterine lumen to coated pits. The endocytotic vesicles thus formed are transported to the lateral membrane and empty into the intercellular spaces by exocytosis 25. From here the immunoglobulins are presumed to reach fetal capillaries. Protein cannot move directly into the intercellular spaces because of the tight junctions near the apex of the cells 25. In addition to this mechanism for conferring passive immunity to the fetus, there is nonspecific uptake of protein from the uterine lumen. Many endocytotic vesicles fuse with larger vacuoles that form part of the cell's lysosomal apparatus 26. The protein they contain is thought to provide amino acids to the fetus. Given the similarity in ultrastructure, these mechanisms are likely to operate in the yolk sac placenta of paca.

In conclusion, the placenta of the paca conforms to patterns previously described for hystricomorph rodents 314. Common features include the lobulation of the placenta and the presence of a subplacenta. At the ultrastructural level they comprise the haemomonochorial nature of the interhaemal barrier and the pinocytotic apparatus of the visceral yolk sac endoderm. The lobulated structure of the placenta allows for a larger exchange area and the development of precocial young 14.

Recently it was argued that more attention should be given to the hystricomorph rodents as models in human medicine. They bear a closer genetic similarity to humans than do murid rodents, such as the mouse and rat, because the latter have undergone a very high rate of gene mutation 27. Since the paca carries a singleton fetus with a birth weight of 640–900 g, it deserves particular consideration as a potential model of fetal growth and development 28.