The principles of classification and a classification of mammals. Bulletin of the AMNH ; v. 85

The excitement and controversy surrounding the potential role of human embryonic stem (ES) cells in transplantation therapy have often overshadowed their potentially more important use as a basic research tool for understanding the development and function of human tissues. Human ES cells can proliferate without a known limit and can form advanced derivatives of all three embryonic germ layers. What is less widely appreciated is that human ES cells can also form the extra-embryonic tissues that differentiate from the embryo before gastrulation. The use of human ES cells to derive early human trophoblast is particularly valuable, because it is difficult to obtain from other sources and is significantly different from mouse trophoblast. Here we show that bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor-beta (TGF-beta) superfamily, induces the differentiation of human ES cells to trophoblast. DNA microarray, RT-PCR, and immunoassay analyses demonstrate that the differentiated cells express a range of trophoblast markers and secrete placental hormones. When plated at low density, the BMP4-treated cells form syncytia that express chorionic gonadotrophin (CG). These results underscore fundamental differences between human and mouse ES cells, which differentiate poorly, if at all, to trophoblast. Human ES cells thus provide a tool for studying the differentiation and function of early human trophoblast and could provide a new understanding of some of the earliest differentiation events of human postimplantation development.

BMP4 initiates human embryonic stem cell differentiation to trophoblast.

The Uterine Spiral Arteries In Human Pregnancy: Facts and Controversies

To discover interordinal relationships of living and fossil placental mammals and the time of origin of placentals relative to the Cretaceous-Paleogene (K-Pg) boundary, we scored 4541 phenomic characters de novo for 86 fossil and living species. Combining these data with molecular sequences, we obtained a phylogenetic tree that, when calibrated with fossils, shows that crown clade Placentalia and placental orders originated after the K-Pg boundary. Many nodes discovered using molecular data are upheld, but phenomic signals overturn molecular signals to show Sundatheria (Dermoptera + Scandentia) as the sister taxon of Primates, a close link between Proboscidea (elephants) and Sirenia (sea cows), and the monophyly of echolocating Chiroptera (bats). Our tree suggests that Placentalia first split into Xenarthra and Epitheria; extinct New World species are the oldest members of Afrotheria.

http://science.sciencemag.org/content/sci/339/6120/662.full.pdf

The Placental Mammal Ancestor and the Post–K-Pg Radiation of Placentals

In mammals, the insulin receptor (IR) gene has acquired an additional exon, exon 11. This exon may be skipped in a developmental and tissue-specific manner. The IR, therefore, occurs in two isoforms (exon 11 minus IR-A and exon 11 plus IR-B). The most relevant functional difference between these two isoforms is the high affinity of IR-A for IGF-II. IR-A is predominantly expressed during prenatal life. It enhances the effects of IGF-II during embryogenesis and fetal development. It is also significantly expressed in adult tissues, especially in the brain. Conversely, IR-B is predominantly expressed in adult, well-differentiated tissues, including the liver, where it enhances the metabolic effects of insulin. Dysregulation of IR splicing in insulin target tissues may occur in patients with insulin resistance; however, its role in type 2 diabetes is unclear. IR-A is often aberrantly expressed in cancer cells, thus increasing their responsiveness to IGF-II and to insulin and explaining the cancer-promoting effect of hyperinsulinemia observed in obese and type 2 diabetic patients. Aberrant IR-A expression may favor cancer resistance to both conventional and targeted therapies by a variety of mechanisms. Finally, IR isoforms form heterodimers, IR-A/IR-B, and hybrid IR/IGF-IR receptors (HR-A and HR-B). The functional characteristics of such hybrid receptors and their role in physiology, in diabetes, and in malignant cells are not yet fully understood. These receptors seem to enhance cell responsiveness to IGFs.

Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease

Animal models of human placentation - : A review

Based on the number of tissues separating maternal from fetal blood, placentas are classified as epitheliochorial, endotheliochorial or hemochorial. We review the occurrence of these placental types in the various orders of eutherian mammals within the framework of the four superorders identified by the techniques of molecular phylogenetics. The superorder Afrotheria diversified in ancient Africa and its living representatives include elephants, sea cows, hyraxes, aardvark, elephant shrews and tenrecs. Xenarthra, comprising armadillos, anteaters and sloths, diversified in South America. All placentas examined from members of these two oldest superorders are either endotheliochorial or hemochorial. The superorder Euarchontoglires includes two sister groups, Glires and Euarchonta. The former comprises rodents and lagomorphs, which typically have hemochorial placentas. The most primitive members of Euarchonta, the tree shrews, have endotheliochorial placentation. Flying lemurs and all higher primates have hemochorial placentas. However, the lemurs and lorises are exceptional among primates in having epitheliochorial placentation. Laurasiatheria, the last superorder to arise, includes several orders with epitheliochorial placentation. These comprise whales, camels, pigs, ruminants, horses and pangolins. In contrast, nearly all carnivores have endotheliochorial placentation, whilst bats have endotheliochorial or hemochorial placentas. Also included in Laurasiatheria are a number of insectivores that have many conserved morphological characters; none of these has epitheliochorial placentation. Consideration of placental type in relation to the findings of molecular phylogenetics suggests that the likely path of evolution in Afrotheria was from endotheliochorial to hemochorial placentation. This is also a likely scenario for Xenarthra and the bats. We argue that a definitive epitheliochorial placenta is a secondary specialization and that it evolved twice, once in the Laurasiatheria and once in the lemurs and lorises.

/pdf/comparative-aspects-of-trophoblast-development-and-1ratypaynt.pdf

Comparative aspects of trophoblast development and placentation.

Placenta has a wide range of functions. Some are supported by novel genes that have evolved following gene duplication events while others require acquisition of gene expression by the trophoblast. Although not expressed in the placenta, high-affinity fetal hemoglobins play a key role in placental gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from mother to fetus is maintained by expression of classic sugar and amino acid transporters at the trophoblast microvillous and basal membranes. In contrast, placental peptide hormones have arisen largely by gene duplication, yielding for example chorionic gonadotropins from the luteinizing hormone gene and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation.

Evolution of Placental Function in Mammals: The Molecular Basis of Gas and Nutrient Transfer, Hormone Secretion, and Immune Responses

Spatial and temporal patterns of expression of messenger RNA for insulin-like growth factors and their binding proteins in the placenta of man and laboratory animals.

Analysis of molecular data sets has provided new insights into higher-level relationships of living Eutheria, including the recognition of Afrotheria as a novel taxon. This offers an opportunity to take a fresh look at the evolution of organ systems, including some that are little used in traditional systematics. In the present study, we attempted a reconstruction of the evolution of characters associated with placentation, the fetal membranes and the female reproductive tract. The evolutionary history of 21 characters has been traced, based on a current hypothesis of eutherian relationships, by applying the computer program MacClade. Accordingly, the analysis provides a first comprehensive interpretation of the stem species pattern of Eutheria. Of particular note, this pattern includes an endotheliochorial chorioallantoic placenta. The reconstructed pattern of Eutheria does not change in the basal nodes of the group. Thus, no character transformations occur on the stem lineages of Laurasiatheria or Euarchontoglires, and even Afrotheria has mostly plesiomorphic character conditions. However, two character transformations occur on the common stem lineage of Afrotheria and its sister taxon Xenarthra, i.e., amniogenesis by cavitation instead of folding and the precocial state of the newborn. In addition, we recognized one character transformation on the stem lineage of Afrotheria, i.e., the occurrence of a four-lobed allantoic sac. Thus, contrary to previous assertions, it is possible to identify morphological characters that could be synapomorphic for this novel taxon.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jez.b.21079

Anthony M. Carter

Papers

Animal models of human placentation - : A review

Comparative aspects of trophoblast development and placentation.

Evolution of Placental Function in Mammals: The Molecular Basis of Gas and Nutrient Transfer, Hormone Secretion, and Immune Responses

Spatial and temporal patterns of expression of messenger RNA for insulin-like growth factors and their binding proteins in the placenta of man and laboratory animals.

Evolutionary transformations of fetal membrane characters in Eutheria with special reference to Afrotheria