Classics revisited: C. J. van der Horst on pregnancy and menstruation in elephant shrews.

BACKGROUND: Menstruation occurs only in higher primates, some bats, the spiny mouse and the elephant shrew. Our knowledge of the latter species is due to work by C. J. van der Horst. FINDINGS: Changes in the uterine stroma are initially similar in fertile and infertile cycles and are confined to a small area. In pregnant animals, the presence of the conceptus causes further development to an implantation chamber. In infertile cycles an outgrowth of highly glandular stroma (a polyp) appears. With decline of the corpora lutea it is shed in a process equivalent to menstruation. Van der Horst described the further development of the placenta and a decidua pseudocapsularis in pregnant animals. In addition he built a unique collection that has thrown light on embryonic development and placentation in other South African mammals. CONCLUSIONS: The changes in endometrial stromal cells during the menstrual cycle appear similar between primates and the elephant shrew and deserve to be studied at the molecular level.

Classics revisited: Miguel Fernández on germ layer inversion and specific polyembryony in armadillos.

BACKGROUND: Miguel Fernández was an Argentinian zoologist who published the first account of obligate polyembryony in armadillos. His contribution is here discussed in relation to his contemporaries, Newman and Patterson, and more recent work. FINDINGS: Fernandez worked on the mulita (Dasypus hybridus). He was able to get early stages before twinning occurred and show it was preceded by inversion of the germ layers. By the primitive streak stage there were separate embryonic shields and partition of the amnion. There was, however, a single exocoelom and all embryos were enclosed in a common set of membranes comprising chorion towards the attachment site in the uterine fundus and inverted yolk sac on the opposite face. He showed that monozygotic twinning did not occur in another armadillo, the peludo (Chaetophractus villosus). CONCLUSIONS: Fernández's work represented a major breakthrough in understanding how twinning occurred in armadillos. His work and that of others is of intrinsic interest to zoologists and has a direct bearing on the origin of monozygotic twins and birth defects in humans.

Classics revisited: Dietrich Starck on comparative embryology and placentation.

BACKGROUND: Dietrich Starck (1908-2001) was a German embryologist who wrote extensive reviews on comparative placentation. FINDINGS: Starck's embryology textbook and his comprehensive review of comparative embryology and placentation give excellent insights into the foundational literature and are extensively referenced. The many original illustrations include placentas from species that are not well described elsewhere. CONCLUSIONS: These resources are especially valuable as a portal to the early literature on comparative placentation.

Placentation in the colugos Cynocephalus volans and Galeopterus variegatus (Dermoptera) and the transition from labyrinthine to villous placentation in primates.

INTRODUCTION: Phylogenetics and genomics place colugos as the sister group to primates. Therefore their placentation is of interest in an evolutionary perspective. Previous accounts are fragmentary, not readily accessible and sometimes contradictory. METHODS: We have examined archival material covering the early development of fetal membranes and placenta, the fate of the yolk sac and definitive placentation. RESULTS: Initially the trophoblast extended over a rather broad but shallow area, enclosing maternal blood spaces. After expansion of the exocoelom it became covered by somatic mesoderm. The mature chorioallantoic placenta was haemochorial and characterized by a labyrinth with markedly dilated maternal blood spaces. Blood vessels appeared in the splanchnopleure early in development and later extended to the yolk sac, but we found no evidence of a choriovitelline placenta at any stage of gestation. There was, however, an extensive paraplacenta. CONCLUSIONS: A choriovitelline placenta is not formed early in gestation nor is it present at term. Early in development invasive trophoblast spreads laterally to form a trophoblastic plate. We found evidence to support the idea that the colugo placenta is intermediate between the labyrinthine placenta of rodents and the trabecular type of Neotropical primates.

The role of the placenta in the initiation of spiral artery remodelling in an early pregnant chimpanzee uterus.

INTRODUCTION: In this study we evaluated the full extent of placental bed changes (centre to periphery) in a pregnant chimpanzee uterus, kept at the Museum for Central Africa in Tervuren, Belgium. According to placental size the specimen was equivalent to an 8 weeks pregnant human uterus. METHODS: Histological sections from central to peripheral tissue blocks of the placental bed were stained to reveal the presence of trophoblast, endothelium, vascular smooth muscle and elastic laminae. As an indicator for early arterial remodelling, we evaluated endothelial nuclear rounding and subendothelial vascular changes within the maternal vasculature in decidua and adjacent inner myometrium. RESULTS: While interstitially invading trophoblasts were present, endovascular trophoblast invasion seemed about to start into one spiral artery outlet at the centre of the placental bed, confirming our previous impression of a later onset of endovascular trophoblast invasion as compared to the human. An early sign of spiral artery remodelling was rounding of the endothelial nuclei. This phenomenon was not related to the local presence of interstitial trophoblast. DISCUSSION: Endothelial nuclear rounding turned out to be a feature of the placental bed as a whole, being significantly less prominent in the adjacent non-placental bed part of the uterus, indicating an effect of the presence of the placenta. The different time-course of early spiral artery remodelling in the chimpanzee as compared to the human may have had a significant impact upon our evolution.

Morphology, histochemistry and glycosylation of the placenta and associated tissues in the European hedgehog (Erinaceus europaeus).

INTRODUCTION: There are few descriptions of the placenta and associated tissues of the European hedgehog (Erinaceus europaeus) and here we present findings on a near-term pregnant specimen. METHODS: Tissues were examined grossly and then formalin fixed and wax-embedded for histology and immunocytochemistry (cytokeratin) and resin embedded for lectin histochemistry. RESULTS: Each of four well-developed and near term hoglets displayed a discoid, haemochorial placenta with typical labyrinth and spongy zones. In addition there was a paraplacenta incorporating Reichert's membrane and a largely detached yolk sac. The trophoblast of the placenta contained diverse populations of granule which expressed most classes of glycan. Intercellular membranes were also glycosylated and this tended to be heavier in the labyrinth zone. Fetal capillary endothelium had glycosylated apical surfaces expressing sialic acid and various other glycans. Glycogen was present in large cells situated between the spongy zone and the endometrium. Trophoblast cells in the placental disc and under Reichert's membrane, as well as yolk sac endoderm and mesothelium, were cytokeratin positive. Reichert's membrane was heavily glycosylated. Yolk sac inner and outer endoderm expressed similar glycans except for N-acetylgalactosamine residues in endodermal acini. DISCUSSION: New features of near-term hedgehog placenta and associated tissues are presented, including their glycosylation, and novel yolk sac acinar structures are described. The trophoblast of the placental disc showed significant differences from that underlying Reichert's membrane while the glycan composition of the membrane itself showed some similarity to that of rat thereby implying a degree of biochemical conservation of this structure.

Early studies of placental ultrastructure by electron microscopy.

BACKGROUND: Transmission electron microscopy (TEM) was first applied to study placental ultrastructure in the 1950's. We review those early studies and mention the scientists that employed or encouraged the use of TEM. FINDINGS: Among the pioneers Edward W. Dempsey was a key figure who attracted many other scientists to Washington University in St. Louis. Work on human placental ultrastructure was initiated at Cambridge and Kyoto whilst domestic animals were initially studied by Björkman in Stockholm and electron micrographs of bat placenta were published by Wimsatt of Cornell University. CONCLUSIONS: Prior to the introduction of better fixation techniques, TEM images were of modest technical quality. Nevertheless they gave important insights into placental ultrastructure, particularly the nature of the maternal-fetal interface.

Placentation in mammals: Definitive placenta, yolk sac, and paraplacenta.

An overview is given of variations in placentation with particular focus on yolk sac, paraplacenta, and other structures important to histotrophic nutrition. The placenta proper varies in general shape, internal structure, and the number of tissues in the interhemal barrier. Yolk sac membranes persist to term in insectivores, colugos, rodents, and lagomorphs. In the latter two orders, they are of known importance for maternal-fetal transfer of antibodies, vitamins, lipids, and proteins. The detached yolk sac of bats is also active throughout gestation. A vascular paraplacenta, or smooth chorioallantois, has known functions in ruminants and carnivores and is found in several other orders of mammal where its function has yet to be explored. In human gestation, the chorion (avascular chorioallantois) is important for hormone synthesis. The true chorion of squirrels and hedgehogs is avascular but may nevertheless allow transfer from mother to fetus through the exocelom. Hemophagous areas with columnar trophoblast are paraplacental structures in carnivores and elephants but occur also within the placenta as in hyenas and moles. In shrews, it is the yolk sac that ingests and processes red cells. Areolas and chorionic vesicles are other structures important for absorption of uterine secretions and ingestion of cellular debris. In conclusion, we find that paraplacental structures, while showing less variation than the placenta proper, contribute not just to the integrity of overall placentation, but in various ways to maternal-fetal interrelationships.

Emil Selenka on the embryonic membranes of the mouse and placentation in gibbons and orangutans.

BACKGROUND: Emil Selenka made important contributions to embryology in marsupials, rodents and primates that deserve wider recognition. Here we review his work on early development of the mouse and placentation in the great apes. FINDINGS: Selenka was intrigued by germ layer theory, which led him to study inversion of the germ layers in the mouse and other rodents. He found it was growth of the ectoplacental cone that caused a downward shift in the position of the underlying ectoderm and endoderm, leading to an inside-outside inversion of these layers. In primates he made the important discovery that the embryos of gibbons and orangutans develop under a decidua capsularis. Thus all great apes, including humans, exhibit interstitial implantation; this is in contrast to other primates where implantation is superficial. CONCLUSIONS: Selenka's work was thorough and brilliantly illustrated. It was an important influence on his contemporaries and was well known to scientists of the following generation. Embryologists continue to advance our knowledge of fetal membranes and placentation in the mouse, but Selenka's work on gibbons is unique and our knowledge of orangutan placentation is restricted to his specimens.

IFPA Senior Award Lecture: Mammalian fetal membranes.

BACKGROUND: Fetal membrane development varies greatly across mammals with significant implications for models of human placentation. METHOD: Therefore the major patterns of fetal membrane development are reviewed with special focus on functions of the inverted yolk sac in murine rodents. FINDINGS: In most mammals, yolk sac and chorion form a choriovitelline placenta to support the early embryo, although this soon is supplanted by a chorioallantoic placenta. Human and haplorrhine primates follow a second pattern where precocious development of the extraembryonic mesoderm leads to formation of a secondary yolk sac within the exocoelom. In rodents there is an inverted visceral yolk sac that encloses the embryo and amnion and functions as an accessory to the chorioallantoic placenta through term. Where present, the inverted yolk sac performs a number of functions that in human are assumed by the syncytiotrophoblast of the chorioallantoic placenta. These include transfer of passive immunity, iron, cobalamin and lipoprotein; protein and lipid synthesis; haematopoiesis; and germ cell storage. Most mammals have a large, fluid-filled allantoic cavity. This is not the case in human and haplorrhine primates where there is an allantoic stalk but no allantoic cavity. Some rodents have a small allantoic cavity, but the mouse and other murine rodents do not. The evolution of amnion, yolk sac and allantois is explored. CONCLUSIONS: Fetal membranes deserve close attention. In particular, the mouse model is incomplete unless the yolk sac is studied along with the chorioallantoic placenta.

IFPA Meeting 2013 Workshop Report II: use of 'omics' in understanding placental development, bioinformatics tools for gene expression analysis, planning and coordination of a placenta research network, placental imaging, evolutionary approaches to understanding pre-eclampsia.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At the IFPA meeting 2013 twelve themed workshops were presented, five of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of new technologies for placenta research: 1) use of 'omics' in understanding placental development and pathologies; 2) bioinformatics and use of omics technologies; 3) planning and coordination of a placenta research network; 4) clinical imaging and pathological outcomes; 5) placental evolution.

A new form of rodent placentation in the relict species, Laonastes aenigmamus (Rodentia: Diatomyidae).

INTRODUCTION: The Laotian rock rat is a relict species in a sister group relationship to hystricognath rodents (Hystricognathi). We asked whether there were similarities in placentation that might reflect this relationship or differences that might cast light on the evolution of Hystricognathi. METHODS: We examined the reproductive tract of nonpregnant (n = 5), early (n = 3) and mid to late gestation (n = 2) females. Selected characters were mapped to a phylogenetic tree to examine their evolution in rodents. RESULTS: The chorionic placenta was discoid and labyrinthine with a spongy zone but without internal lobes. The interhemal region was hemodichorial with syncytiotrophoblast lining maternal blood spaces and an inner layer of vacuolated cytotrophoblast. There was no subplacenta. The yolk sac was well developed with a villous portion that faced the placental disk but no fibrovascular ring. There was a single fetus that very likely would be precocial at birth. DISCUSSION: A lobulated labyrinth and the presence of a subplacenta and a fibrovascular ring emerged as synapomorphies for Hystricognathi. Laonastes, Ctenodactylus and stem Hystricognathi all had precocial young, whereas altriciality was the plesiomorphic condition for rodents. A hemomonochorial interhemal region was plesiomorphic for rodents and Hystricognathi, and the hemodichorial condition found in Laonastes, and possibly in Ctenodactylus, was unlike that of any rodent studied to date. CONCLUSION: Similar to Hystricognathi, Laonastes bears precocial young, but this species lacks placental adaptations such as the subplacenta, suggesting they were evolved subsequent to a change in reproductive strategy in the common ancestor of Laonastes and Hystricognathi.

IFPA Meeting 2012 Workshop Report I: comparative placentation and animal models, advanced techniques in placental histopathology, human pluripotent stem cells as a model for trophoblast differentiation.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2012 there were twelve themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of models and technical issues involved in placenta research: 1) comparative placentation and animal models; 2) advanced techniques in placental histopathology; 3) human pluripotent stem cells as a model for trophoblast differentiation.

An unusual feature of yolk sac placentation in Necromys lasiurus (Rodentia, Cricetidae, Sigmodontinae).

We studied the development of the inverted yolk sac in a New World rodent, Necromys lasiurus during early placentation. Ten implantation sites were investigated by means of histology, immunohistochemistry and electron microscopy. The yolk sac was villous near its attachment to the placenta. Elsewhere it was non-villous and closely attached to the uterus. The uterine glands were shallow and wide mouthed. They were associated with vessels and filled with secretion, suggesting the release of histotroph. This feature was absent at later stages. The intimate association of the yolk sac with specialized glandular regions of the uterus may represent a derived character condition of Necromys and/or sigmodont rodents.

Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?

The implantation of the blastocyst and early development of the placenta are crucial for the success of implantation and pregnancy. However, the formative stages of human placental development are largely unknown because of their existence in a 'black box' where access to samples is extremely limited for ethical reasons. In this review we discuss our current knowledge of early placental formation from the time of implantation at 3 weeks of gestation to approximately 5-6 weeks of gestation, encompassing both the significant anatomical findings derived from the unique specimens obtained in the mid-20th century and the renewed study of this period over the past 10 years as novel models of implantation have been developed.

The evolving placenta: convergent evolution of variations in the endotheliochorial relationship.

Endotheliochorial placentas occur in orders from all four major clades of eutherian mammal. Species with this type of placenta include one of the smallest (pygmy shrew) and largest (African elephant) land mammals. The endotheliochorial placenta as a definitive form has an interhemal area consisting of maternal endothelium, interstitial lamina, trophoblast, individual or conjoint basal laminas, and fetal endothelium. We commonly think of such placentas as having hypertrophied maternal endothelium with abundant rough endoplasmic reticulum (rER), and as having hemophagous regions. Considering them as a whole, the trophoblast may be syncytial or cellular, fenestrated or nonfenestrated, and there may or may not be hemophagous regions. Variations also appear in the extent of hypertrophy of the maternal endothelium and in the abundance of rER in these cells. This combination of traits and a few other features produces many morphological variants. In addition to endotheliochorial as a definitive condition, a transitory endotheliochorial condition may appear in the course of forming a hemochorial placenta. In some emballonurid bats the early endotheliochorial placenta has two layers of trophoblast, but the definitive placenta lacks an outer syncytial trophoblast layer. In mollosid bats a well developed endotheliochorial placenta is present for a short time even after a definitive hemochorial placenta has developed in a different region. It is concluded that the endotheliochorial placenta is more widespread and diversified than originally thought, with the variant with cellular trophoblast in particular appearing in several species studied recently.

Human placentation from nidation to 5 weeks of gestation. Part II: Tools to model the crucial first days.

Human pregnancy is unusual with respect to monthly spontaneous decidualisation as well as the degree of placental invasion and interaction with the decidualised endometrial stroma. This review covers in vivo animal models and in vitro cell culture models that have been used to study the earliest stages of human implantation and placentation from nidation to 5 weeks of gestation. The field has expanded rapidly in recent years due to the generation of human embryonic stem cell lines and the ability of some scientists to culture human blastocysts. These models have enabled researchers to begin to elucidate the interactions involved in human blastocyst apposition, adhesion and implantation. However, we still understand very little about the differentiation processes involved in the formation of the placenta. Continued improvements to current models, including the potential isolation of a human trophoblast stem cell, will significantly enhance our ability to define the molecular and structural events occurring during human implantation and early placental development.