Yolk Sac Placenta Research Articles

92-kDa gelatinase (matrix metalloproteinase-9) is induced in rat amnion immediately prior to parturition.

The fetal membranes undergo striking changes in structure before delivery that involve catabolism of the extracellular matrix. To investigate the role of specific enzymes in this process, we examined gelatinase activities in rat amnion, visceral yolk sac placenta, and placenta and amniotic fluid between Days 18-21 of pregnancy. Matrix metalloproteinase (MMP)-2 was present in amnion on all days, and its activity increased slightly on Day 21. The 92-kDa gelatinase, MMP-9, was not detected on Days 18-20 but appeared by the morning of Day 21. There was a marked increase in MMP-9 mRNA in the amnion on Day 20, preceding the appearance of MMP-9 activity. Western blotting confirmed an increase in MMP-9 protein in amnion on Day 21. MMP-2 and MMP-9 activities were detected in extracts of whole yolk sac placenta, placenta, and amniotic fluid, but there were no striking changes in these gelatinases between Days 18 and 21. However, the capsular regions of the visceral yolk sac placentae, which thin and rupture during labor, did show higher MMP-9 activity on Day 21 than on Days 18 and 20. We suggest that the striking increase in MMP-9 expression in amnion and possibly the capsular region of the visceral yolk sac placenta approximately 12 h prior to delivery is responsible, in part, for the alterations in the structure of these fetal membranes before parturition.

Development of a Physiologically Based Pharmacokinetic Model Describing 2-Methoxyacetic Acid Disposition in the Pregnant Mouse

Using the potent developmental toxicant 2-methoxyethanol (2-ME) as a prototypical compound, a physiologically based pharmacokinetic (PBPK) model was developed to describe the disposition of its primary metabolite and proximate toxicant 2-methoxyacetic acid (2-MAA) in the pregnant CD-1 mouse. Data were collected during early, mid, and late organogenesis, specifically Gestation Days (GD) 8, 11, and 13 (GD 0 = plug-positive date). Pharmacokinetics and tissue partition coefficients for 2-MAA were determined in maternal plasma and conceptus on GD 8 and in maternal plasma, embryo, and extraembryonic/amniotic fluid (EAF) on GD 11 and 13. For simulation of GD 8 data, the conceptus was described as a single compartment, combining the yolk sac placenta, embryo, EAF, and decidua. For GD 11 and 13, the placenta, embryo, and EAF were explicitly described. Several hypotheses were tested for their ability to predict 2-MAA dosimetry. These hypotheses were encoded as alternative models having (a) blood flow-limited delivery of 2-MAA to model compartments, (b) pH trapping of ionized 2-MAA within compartments, (c) active transport of 2-MAA into compartments, and (d) reversible binding of 2-MAA within compartments. While the flow-limited description adequately predicted GD 8 dosimetry, the best simulations of the pharmacokinetic data collected on GD 11 and 13 were obtained with the active transport models. Since the mechanism by which 2-MAA accumulates into the embryo and EAF has not yet been elucidated, these mathematical descriptions are empirical. Further development of this PBPK model for 2-MAA in pregnant mice, in particular its scale-up to humans, will facilitate more realistic human risk assessments for the developmental toxicity of 2-ME and related compounds.

Placental structure of the Australian lizard, Niveoscincus metallicus (Squamata: Scincidae).

A unique type of reptilian allantoplacenta was described by Weekes [1930] (Proc. Linn. Soc. N.S.W. 55:550-576) from a single embryonic stage of the Tasmanian skink, Niveoscincus ocellatus (as Lygosoma (Liolepisma) ocellatum). She also assigned N. metallicus to this placental category but did not provide a description. Here we provide a description of allantoplacentation and yolk sac placentation of N. metallicus. The allantoplacenta is regionally differentiated and differs from other reptilian allantoplacentae by the presence of a zone of hypertrophied chorionic epithelial cells in apposition to uterine blood vessels which are contained within ridges formed from uterine epithelial cells. This zone is located dorsolaterally along the long axis of the egg at the upper margin of the yolk sac. In contrast, the cells of the chorionic epithelium dorsal to the embryo are smaller and the uterine blood vessels are not contained in ridges. The definitive yolk sac placenta is an omphaloplacenta. The bilaminar omphalopleure of the omphaloplacenta consists of an outer layer of cuboidal or columnar cells. Cells of the uterine epithelium of the omphaloplacenta are cuboidal or columnar in shape and are supported by uterine blood vessels. © 1994 Wiley-Liss, Inc.

Endoderm cells of the equine yolk sac from Day 7 until formation of the definitive yolk sac placenta

SummaryOn Day 7 of pregnancy, when the inner cell mass coalesces to one side of the blastocyst, a discontinuous layer of cells is present underlying the inner cell mass and isolated cells were found around the mural trophoblast. As early as Day 8, these cells that were scattered around the blastocyst cavity unite to form a continuous endodermal layer, resulting in a bilaminar blastocyst. The endodermal cells have slightly bulging apical surfaces towards the cavity of the blastocyst, but in many areas have flanges and projections that form complex basolateral compartments within the endoderm and especially between the endoderm and trophoblast. These cells also develop an extensive series of unusual apical ridges. With the development of the primitive streak and the trilaminar blastocyst, angiogenesis proceeds from the forming embryo into the yolk sac. At first the anastomotic vessels form a simple mesh, but by Day 20, erythroblasts are present in the newly formed sinus terminalis. The loss of the capsule (Day 21) and the development of the embryonic circulation establish the relationships of the definitive yolk sac. There is a bilaminar region with endodermal cells showing basolateral compartmentalisation and a specialised sinus terminalis region bordering the choriovitelline placenta. The largest endodermal cells are associated with the choriovitelline placenta, but a substantial cuboidal lining also covers the splanchnopleuric portion of the vascular yolk sac. The allantochorion rapidly assumes predominance in respiratory exchanges, and the choriovitelline placenta not only decreases in relative area but increases in thickness. However, the 3 major regions of the yolk sac persist for several weeks after their formation, and both the vasculature and especially the endodermal cells remain robust despite the decrease in size of the yolk sac. It is concluded that the pleomorphic endodermal cells of the equine yolk sac differentiate in response to local signals. By Day 25 the allantochorion is an increasingly significant exchange unit, and the continued robustness of the vascular portions of the yolk sac and especially its endodermal layer suggests that synthetic and metabolic activities of the endodermal cells will be the dominant function of the yolk sac subsequently.

Ontogeny of the umbilical cord and placenta in the Atlantic sharpnose shark,Rhizoprionodon terraenovae

The Atlantic sharpnose shark is a viviparous anamniote that develops an epitheliochorial yolksac placenta. Initially, contents of the yolksac nourish the embryos. Yolk is partially digested in the yolk syncytial-endoderm complex and subsequently transferred to the vitelline circulation. Yolk is also transported by ciliary activity of the yolk stalk ductus to the fetal gut for digestion. When embryos are 4.0cm in length, vascular ridges, termed appendiculae, develop on the yolk stalk. As yolk stores are depleted, the yolksac differentiates into the fetal portion of the placenta and the uterus abutting the yolksac differentiates into the maternal portion of the placenta. The yolk stalk differentiates into an elongate umbilical cord. The uterine epithelium produces secretions that are positive by the periodic acid-Schiff and alcian blue methods and metachromatic when stained with toluidine blue. Uterine capillaries are continuous and the surface epithelium is active both in secretion and transport of nutrients. When the embryos are 7–10cm in length, appendiculae are elongate, branched and populated by separate microvillar and granulated cells. Appendiculae may function as a paraplacental nutrient absorptive organ and be involved in the regulation of osmolarity of periembryonic fluids. The fetal placenta has two functional regions: a proximal portion that is presumed to function as a steroid producing organ and a distal portion that effects nutrient and metabolic exchange between the mother and fetus. Characteristics of the fetal placenta include endocytotic activity, crystalline-like cytoplasmic bodies and fenestrated capillaries. Fetal and maternal components of the placenta are separated by the egg envelope.

Histology of the late-stage placentae in the matrotrophic skink Chalcides chalcides (Lacertilia; Scincidae).

Examination of late-stage placental material of the lizard Chalcides chalcides from the Hubrecht Laboratorium (Utrecht, The Netherlands) reveals several cytological and histological specializations that appear to have been superimposed over a morphological pattern that is typical for squamates. The chorioallantoic placenta is highly vascularized and consists of a single mesometrial placentome and a generalized paraplacentomal region, both of which are epitheliochorial. The placentome is deciduate, and contains deeply interdigitating folds of hypertrophied uterine and chorioallantoic tissue. Chorionic epithelium lining the placentome comprises enlarged, microvilliated cells, a small proportion of which are diplokaryocytes. The placentomal uterine epithelium is not syncytial and consists of enlarged cells bearing microvilli. The yolk sac placenta is a true omphaloplacenta (sensu stricto), being formed by juxtaposition of uterine tissues to an avascular, bilaminar omphalopleure. Epithelium of the omphalopleure is stratified and is hypertrophied into papillae that project into detritus of the uterine lumen. The omphalopleure is separated from the yolk sac proper by a yolk cleft that is not confluent with the exocoelom and is not invaded by the allantois. Neither an omphalallantoic placenta nor a true choriovitelline placenta is present in late gestation. Morphologically, the mature placentae of C. chalcides are among the most specialized to have been described in reptiles, reflecting the substantial maternal-fetal nutrient transfer that occurs in this species. © 1993 Wiley-Liss, Inc.

Differences in binding characteristics of rat and human transferrin by rat visceral yolk sac placenta

Previous work has shown that human serum supplemented with rat transferrin can support the normal growth of cultured rat conceptuses, but that supplementation with human transferrin has no such effect. Such results strongly suggest an hypothesis of species-specificity. This potential specificity was therefore investigated by comparing uptake, binding, competition and vectorial transport of both rat and human transferrin using two well-established systems, those of 17.5 day rat visceral yolk sacs and anembryonic yolk sacs in culture. The results of these investigations show that human transferrin displays a lower rate of uptake and lower binding affinity for the rat transferrin receptor than does rat transferrin. Human transferrin competes poorly with rat transferrin for receptor occupancy unless present in 20-fold excess. Both molecules are taken up by receptor-mediated endocytosis and are processed in a similar manner. Anembryonic yolk sac experiments show that a greater proportion of intact rat transferrin is transported to the exocoelomic fluid than is intact human transferrin. Binding analyses show a difference in binding affinities of the two molecules for the rat transferrin receptor and also that human transferrin exhibits negative cooperativity in its binding. This evidence strongly supports an hypothesis of species-specificity in the binding of transferrin to the transferrin receptor in the rat visceral yolk sac.

X-inactivation in marsupials and monotremes

Marsupials (metatherian) and eutherians ('placental') are the two extant groups of live bearing mammals which constitute the Theria, as opposed to the Protheria, or egg-laying monotremes. The current estimates for times of separation are 145 MYR BP for Theria-Prototheria and 130 MYR for marsupial-eutherian. This review focuses mainly upon marsupial X-inactivation, the study of which has revealed differences between marsupials and eutherians in mechanisms of X-inactivation, and in the function of the system in dosage compensation and reproduction. Marsupials resemble eutherians in having inactivation of one of the two X chromosomes in the soma and pre-meiotic germ cells of their females. However, marsupial X-inactivation differs from its eutherian counterpart in two respects: firstly, the paternally derived allele is inactivated, and secondly it is sometimes incomplete. These differences exist despite the fact that the marsupial X is homologous to the human Xq. Data are available for five X-linked loci, four controlling enzyme structure: glucose-6-phosphate dehydrogenase (G6PD), phosphoglycerate kinase 1 (PGK1), alpha-galactosidase (GLA) and hypoxanthine phosphoribosyl transferase (HPRT) and for ribosomal RNA. Both the G6PD and PGK1 loci exhibit partial expression of the paternally derived allele, but the pattern of expression for the two loci differs between tissues and between species. The ribosomal RNA gene clusters are on the X of kangaroos and didelphids, and clusters from both chromosomes are expressed in females. One of the two X chromosomes exhibits late replication, in particular in cells where a paternally derived gene is partly active, demonstrating that late replication and absence of transcription are not necessarily correlated. Female specific sex chromatin bodies are most clearly defined in species with small Y chromosomes. The extra-embryonic (placental) membranes of marsupials also have patterns of inactivation which show species and locus differences. The paternally derived allele at the G6PD locus in yolk sac placenta of a kangaroo was not inactivated but was completely inactivated in all other embryonic tissues. In contrast, in a dasyurid (Australian carnivorous) marsupial, GLA showed complete paternal X-inactivation in all embryonic and extra-embryonic tissues. Although the Y is testis determining in marsupials, it appears that possession of a scrotum or pouch is under X chromosome control; XXY animals are pouched males and XO and XX/XO animals are females with scrota. Whether this is due to a dosage difference or whether it is an imprinting phenomenon remains to be decided. While sex specific differences in methylation of CpG residues have been found in the body of the gene, their role in marsupial X-inactivation is debatable.Monotremes sex chromosomes are difficult to study. The differentiation into X and Y seems to be incomplete. DNA replication studies indicate the possibility of X-inactivation, but demonstration of the phenomenon at the single gene level has not been possible.

The rate of blood flow through the inverted yolk sac placenta of the anaesthetized guinea-pig

The rate of blood flow through the yolk sac placenta of late gestation guinea-pig fetuses was estimated by an indirect approach: radionuclide-labelled microspheres were injected in a saphenous vein and the ratio of radioactivity in the yolk sac to that in one of several reference organs was calculated. The ratio was then multiplied by a constant derived from separate experiments in which blood flows to the fetal abdominal organs and chorioallantoic placenta were determined. Stomach blood flow was positively correlated to arterial oxygen content (r = 0.74, P < 0.05), as was the weight-specific splenic blood flow (r = 0.66, P < 0.05). Perfusion of the small and large bowel, kidneys and chorioallantoic placenta was not related to arterial pH or oxygen content and these organs were used as references for the estimation of vitelline blood flow. A positive correlation was found between yolk sac blood flow and arterial oxygen content (r = 0.91, P < 0.01). In normoxaemic guinea-pig fetuses, yolk sac blood flow is 100-300 microliters per min.

Reflections on the Evolution of Piscine Viviparity

Viviparity first makes its evolutionary appearance within the craniate-vertebrate line among fishes. We estimate that it has independently evolved at least 42 times in five of the nine major groups of fishes. Viviparity is the dominant mode of reproduction among the cartilaginous sharks and rays, i.e., 55% of approximately 900 living species. It is less prevalent among the five major groups of bony fishes, i.e., 2–3% of an estimated 20,000 or more species. The evolution of viviparity from oviparity involves: 1) a shift from external to internal fertilization; 2) retention of embryos in the female reproductive system; 3) utilization of the ovaryor oviduct as sites of gestation; 4) structural and functional modification of the embryo and the female reproductive system and; 5) modification of extant endocrine mechanisms controlling reproduction. Viviparity offers selective advantages to parents and offspring, such as: 1) enhanced survival of offspring; 2) compensation for low fecundity; 3) amplification of reproductive niches to reduce competition; 4) exploitation of pelagic niches; 5) colonization of new habitats; and 6) increased energetic efficiency in viviparous matrotrophes. Its principal disadvantages include: 1) reduced fecundity; 2) cost to the female; and 3) risk of brood loss through maternal death. Acquisition of viviparityestablishes new maternal-embryonic relationships, namely: 1) trophic; 2) osmoregulatory and excretory; 3) respiratory; 4) endocrinological; and 5) immunological. In sharks, rays, and the coelacanth, gestation takes place in the oviduct, but in teleosts gestation occurs either in the ovarian follicle or ovarian lumen. The cystovarian teleostean ovary is hypothesized to function both as ovary and oviduct. Oviductal, ovarian lumenal, andfollicular epithelial cells are the maternal sites of metabolic exchange. Metabolic exchange inembryos takes place across the epithelia of the general body surface and its derivatives or across the gut epithelium and its derivatives. Four patterns of piscine placentation have evolved,namely: 1) yolk sac; 2) follicular; 3) branchial; and 4) trophotaenial placentae. The pericardial amniochorion, the embryonic portion of the follicular placenta, occurs in poeciliids and several other teleostean groups. Developmental, it is nearly identical to the anterior aminochorionic fold of tetrapod vertebrates. Trophotaeniae are external rosette or ribbon-like structuresthat have evolved in four orders of teleosts by heterochrony, i.e., accelerated outgrowth and differentiation of the embryonic hind gut. With the possible exception of the coelacanth, theyolk sac placenta occurs only in sharks. We estimate that it has independently evolved between 11 and 20 times. It displays considerable diversity. Evolution of the yolk sac placenta entails retention of the yolk sac and secondary differentiation of its distal portion for implantation and maternal tissue-embryonic tissue metabolic exchange and its proximal portion for oviductal fluid-embryonic tissue exchange. The yolk stalk lengthens, is modified into an umbilical stalk, and establishes a site of autotomy at the embryo-umbilical stalk junction. The lumenal wall of the oviduct becomes competent to function as a site of implantation.

Comparative Studies of Structure and Function in Mammalian Placentas with Special Reference to Maternal-Fetal Transfer of Iron

The mammalian chorioallantoic placenta is an extremely complex and structurally diverse organ. To better understand the placenta a number of classification schemes have been devised. Classification on the basis of gross form or shape recognizes four major categories—diffuse, cotyledonary, zonary and discoid. Another important classification scheme is based on the number of tissue layers separating the maternal and fetal vascular systems in the placenta. On this basis, three major types of placentas are recognized—epitheliochorial, endotheliochorial and hemochorial. In many species, pathways in addition to the chorioallantoic placenta exist for maternal-fetal exchange. Some species have a yolk sac placenta functioning concurrently with the chorioallantoic placenta whereas in some other species exchange may occur across a chorioamnion. Some species have accessory or paraplacental structures which function in nutrient exchange; these include hemophagous regions and areolae. In the final sections, I review how these different structural specializations come into play to accomplish a particular function, namely that of iron transfer to the fetus. There are at least four different mechanisms by which different species accomplish iron transfer to the fetus. These include 1) absorption of maternal transferrin-bound iron by the placenta; 2) absorption of iron by the yolk sac; 3) phagocytosis of maternal erythrocytes and 4) absorption of iron-rich uterine secretions by accessory placental structures.

A physiologically based kinetic model of rat and mouse gestation: Disposition of a weak acid

A physiologically based toxicokinetic model of gestation in the rat and mouse has been developed. The model is superimposed on the normal growth curve for nonpregnant females. It describes the entire gestation period including the period of organogenesis. The model consists of uterus, mammary tissue, maternal fat, kidney, liver, other well-perfused maternal tissues, and other poorly perfused maternal tissues, embryo/fetal tissues, and yolk sac and chorioallantoic placentas. It takes into account the growth of maternal tissues such as uterus, mammary glands, fat, and liver during pregnancy, as well as growth of the conceptus. The gestation model is based on published values of organ volumes and blood flows for the rat throughout pregnancy. It is scaled to the mouse using conventional scaling procedures. Its descriptive utility has been examined with the test chemical 5,5′-dimethyloxazolidine-2,4-dione (DMO), a weak acid that is not bound measurably in plasma or tissues and is eliminated by excretion in the urine. Concentrations of DMO were monitored in maternal rat and embryo plasma and in homogenates of maternal rat muscle and whole embryo after ip administration at 9:00 am on Day 13 of gestation. On the basis that distribution of DMO is determined solely by its pK and the pH's of body fluids, pH and excretion rate values were estimated by visual optimization of model predictions to the concentration profile. Successful prediction of concentrations of DMO in the same tissues of pregnant mice after its ip administration at 9:00 am on Day 10 or 11 of gestation required only adjustment for pH's of mouse body fluids.

The artificially perfused guinea-pig yolk sac placenta: Transfer and uptake of water, glucose and amino acids

The development of a new technique to investigate maternal fetal transfer across the near term guinea pig yolk sac placenta by in-situ perfusion of the yolk sac vessels is described. The maternal fetal transfer of labeled water, d- and l-glucose, O-methyl- d-glucose (oMDG), d- and l-alanine, d- and l-aspartate, L-lactate and alphaamino- isobutyric acid (AIBA) was investigated after injection of these substances into the maternal circulation. After 15 min of perfusion at 0.5 ml/min the water clearance was 132 ± 12 μ/ min ( SEM, n = 30). The clearances for d- or l-glucose were less than 1.2,μl/min. The activity of label in the venous yolk sac perfusate of all other substances was not different from background activity when 14C-label was used. The clearance of 3H- l-alanine approached the clearance value of water. The total uptake (as defined for single-injection double tracer dilution experiments) from the perfusate of d-glucose, oMDG, alanine and aspartate in comparison to l-glucose was also studied. Mean d-glucose uptake was 11.2 ± 1.9 per cent ( n = 8), it was significantly reduced to 4.9 ± 2 per cent ( n = 5) by cytochalasin B (1 × 10 −4 mmol/l), and by increasing concentrations of d-glucose (1 to 20 mmol/l, n = 4). The uptake of oMDG was 8.8 ± 1.5 per cent ( n = 8). l-alanine uptake was 25 ± 3.4 per cent, d-alanine uptake was 8.3 ± 1.5 per cent ( n = 12). Both uptake values were decreased significantly by 10 mmol/l l-alanine, but unaffected by [Na +] (< 15 mequ/l). There was no uptake of AIBA. The uptakes of l-aspartate were 34.9 ± 3.7 per cent and oft-aspartate 40.4 ± 4.8 per cent ( n = 11). Both uptake values were significantly and reversibly reduced by 1 mmol/l l-aspartate and d-aspartate, and by low [Na +] (< 15 mequ/l). It is concluded that water can move by diffusion from maternal circulation into the yolk sac capillaries in considerable amounts whereas the contribution of the yolk sac placenta to fetal nutrition with d-glucose, l-alanine and l-aspartate is negligible. The membranes of yolk sac cells contain specific transport systems for d-glucose, d-/l-alanine and d-/l-aspartate transfer. The function of the vitelline placenta in the near-term guinea-pig is comparable more to the gut than to the chorio-allantoic placenta.

Transfer of 22Na+ across the guinea pig yolk sac placenta perfused in situ

Transfer of 22Na+ across the guinea pig yolk sac placenta perfused in situ

Effects of sustained dietary ethanol on the ultrastructure of the visceral yolk‐sac placenta of the rat

The present investigation reports ultrastructural alterations in endodermal epithelial cells of the rat visceral yolk-sac placenta that accompany alcohol-induced changes in intracellular trafficking of endocytosed maternal serum proteins. Fine structural changes include restructuring of mitochondrial cristae (foliate to vesicular and tubular forms), beading of cisterns of granular endoplasmic reticulum, hypertrophy and hyperplasia of Golgi elements, differentiation of the Golgi membranes to a GERL configuration, and a notable increase in numbers of primary lysosomes. Such changes in ultrastructure suggest that exposure of this developing maternofetal exchange system to high levels of ethanol in maternal blood increases the production of primary lysosomes near term for proteolysis of maternal serum proteins within the visceral yolk-sac epithelium. Near term, targeting of endocytosed protein to secondary lysosomes for proteolysis appears to be augmented; transcellular routing of maternal protein (e.g., IgG) for placental transport may be impeded. Thus significance of the observed changes in the fine structure of this placenta may relate to the mechanism(s) of action of maternal alcohol consumption on the acquisition of neonatal immunity, intrauterine growth retardation, and the production of congenital malformations.

Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis

Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis.

Development, morphology, and function of the yolk‐sac placenta of laboratory rodents

A review of current knowledge of the unusual structure and several functions of the yolk-sac membranes of common laboratory rodents, viz., rats, mice, hamsters, guinea pigs and gerbils, enables a better assessment of the significance of this maternofetal exchange system in the experimental production of congenital anomalies. The anatomy of both visceral and parietal walls of the rodent yolk-sac placenta--specifically the anatomical relationships of each wall with maternal and with other fetal tissues--depends on the mode of origin and subsequent development of the yolk sac in these several species. Accordingly, the developmental biology of the rodent yolk sac is described. Since both fine structure and anatomical relationships also determine in large measure the functioning of the membrane as a whole in the absorption of selected materials either for intracellular digestion or for cellular translocation and transport to the developing embryo, the anatomy of the yolk sac is considered in detail. Similarly, since available evidence strongly suggests that teratogenic agents induce perturbations in the cellular mechanisms that control these several functions of the yolk-sac placental system in the production of birth defects, additionally an account is given of the cell biology of the membrane, i.e., endocytosis and targeting/trafficking of materials either for digestion within the epithelium at the maternal surface of the visceral yolk sac or for translocation across the yolk-sac membrane as a whole.

Blastocyst implantation in the chinese hamster (Cricetulus griseus)

Embryonic development of the Chinese hamster (Cricetulus griseus) was studied from the onset of implantation to the formation of the parietal yolk sac placenta. Implantation began on day 6 of pregnancy, when the embryo became fixed to the uterine luminal epithelium. At this time there was no zona pellucida, and microvilli of the trophoblast and uterine epithelium were closely apposed. Stromal cells immediately adjacent to the implantation chamber began to enlarge and accumulate glycogen. By day 7 the mural trophoblast penetrated the luminal epithelium in discrete area. The trophoblast appeared to phagocytize uterine epithelial cells, although epithelium adjoining the points of penetration was normal. In other areas nascent apical protrusions from the uterine epithelium indented the surface of the trophoblast. The epiblast had enlarged and both visceral and parietal endoderm cells were present. The well-developed decidual cells were epithelioid and completely surrounded the implantation chamber. On day 8 the uterine epithelium had disappeared along the mural surface of the embryo. The embryonic cell mass was elongated and filled the yolk sac cavity. Reichert's membrane was well developed. The uterine epithelial basal lamina was largely disrupted, and the trophoblast was in direct contact with decidual cells. Primary and secondary giant trophoblast cells were present and in contact with extravasated maternal blood. The mural trophoblast formed channels in which blood cells were found in close proximity to Reichert's membrane. Decidual cells were in contact with capillary epithelium and in some cases formed part of the vessel wall. Structural changes occurring in the embryo and endometrium during implantation in the Chinese hamster are described for the first time in this report and are compared to those described for some other myomorph rodents.

Immunoglobulin G levels in fetal and newborn tammar wallabies (Macropus eugenii)

Immunoglobulin G (IgG) was measured in fetal, neonatal and colostral samples from the tammar wallaby (Macropus eugenii) in order to study the possibility of passively acquired immunity. Samples were obtained from young at a known stage of gestation and at known times (to the minute) after birth. IgG was present (in increasing levels of concentration) in fetal serum, neonatal serum and colostrum. Since the fetus and neonate are probably unable to make immunoglobulin (Ig), it is hypothesized that transplacental and trans-gut transmission takes place from mother to offspring. The vascular yolk sac placenta has a high concentration of IgG, and is the most likely route of transmission from mother to young. Some observations were made of IgA which was found only in colostrum. No Ig of either kind was found in yolk sac fluid.

D-glucose uptake and transfer in the artificially perfused guinea-pig yolk sac placenta

Dopamine neurons in the substantia nigra pars compacta regulate not only motor but also cognitive functions. NMDA receptors play a crucial role in modulating the activity of these cells. Considering that the amino-acid D-Aspartate has been recently shown to be an endogenous NMDA receptor agonist, the aim of the present study was to examine the effects of D-Aspartate on the functional properties of nigral dopamine neurons. We compared the electrophysiological actions of D-Aspartate in control and D-aspartate oxidase gene (Ddo−/−) knock-out mice that show a concomitant increase in brain D-Aspartate levels, improved synaptic plasticity and cognition. Finally, we analyzed the effects of L-Aspartate, a known dopamine neuron endogenous agonist in control and Ddo−/− mice. We show that D- and L-Aspartate excite dopamine neurons by activating NMDA, AMPA and metabotropic glutamate receptors. Ddo deletion did not alter the intrinsic properties or dopamine sensitivity of dopamine neurons. However, NMDA-induced currents were enhanced and membrane levels of the NMDA receptor GluN1 and GluN2A subunits were increased. Inhibition of excitatory amino-acid transporters caused a marked potentiation of D-Aspartate, but not L-Aspartate currents, in Ddo−/− neurons. This is the first study to show the actions of D-Aspartate on midbrain dopamine neurons, activating not only NMDA but also non-NMDA receptors. Our data suggest that dopamine neurons, under conditions of high D-Aspartate levels, build a protective uptake mechanism to compensate for increased NMDA receptor numbers and cell hyper-excitation, which could prevent the consequent hyper-dopaminergia in target zones that can lead to neuronal degeneration, motor and cognitive alterations.