Review: Toward an integrated evolutionary understanding of the mammalian placenta

Abstract

The placenta is fundamentally important for the success of pregnancy. Disruptions outside the normal range for placental function can result in pregnancy failure and other complications. The anatomy of the placenta varies greatly across mammals, as do key parameters in pregnancy such as neonatal body mass, length of gestation and number of offspring per pregnancy. An accurate understanding of the evolution of the mammalian placenta will require at minimum the integration of anatomical, developmental, physiological, genetic, and epigenetic data. Currently available data suggest that the placenta is a dynamic organ that has evolved rapidly in a lineage specific manner. Examination of the placenta from the perspective of human evolution shows that many anatomical features of the human placenta are relatively conserved. Despite the anatomical conservation of the human placenta there are many recently evolved placenta-specific genes (e.g. CGB, LGALS13, GH2) that are important in the development and function of the human placenta. Other mammalian genomes have also evolved specific suites of placenta-expressed genes. For example, rodents have undergone expansions of the cathepsin and prolactin families, and artiodactyls have expanded their suite of pregnancy-associated glycoproteins. In addition to lineage specific birth and death of gene family members, the pattern of imprinted loci varies greatly among species. Taken together, these studies suggest that a strategy reliant upon the sampling of placentally expressed and imprinted genes from a phylogenetically diverse range of species is appropriate for unraveling the conserved and derived aspects of placental biology.

Fig. 1. Phylogenetic relationships among mammals

This figure depicts the current view of the phylogenetic relationships among major superordinal mammalian clades [–45]. The Eutheria includes all extant placental mammals and is made up of four extantsuperordinal clades: Euarchontoglires (e.g. Primates, Rodentia), Laurasiatheria (e.g. Carnivora, Perrisodactyla), Xenarthra (e.g. Pilosa, Cingulata), and Afrotheria (e.g. Proboscidea, Sirenia). Euarchontoglires joins Laurasiatheria to form Boreoeutheria, and Xenarthra joins Afrotheria to form Atlantogenata. Metatheria refers to the marsupial mammals, and Prototheria includes the egg-laying monotremes.

Fig. 2. Primate gene clusters with placenta-specific expression

The figure depicts the orientation, exon/intron structure, and location of three gene clusters that have genes with placenta-specific expression in anthropoid primates [23,28,29]. These gene families expanded via duplication during primate evolution. A) A cluster of galectins located on human chromosome 19. LGALS14 is expressed only in the placenta, and has been shown to have two splice variants as depicted in the figure. Other genes in this cluster with predominant placenta expression include LGALS13 and LGALS16. B) The chorionic gonadatropin cluster is located on human chromosome 19. Microarray studies [su] demonstrate that he gene encoding the beta peptide of human chorionic gonadotropin (CGB) is highly expressed in the placenta as are CGB5, CGB7, and CGB8. The gene encoding luteinizing hormone, LHB, is found in non-anthropoids. C) The gene cluster containing the human growth hormones/placental lactogens is found on human chromosome 17. Many of these genes have multiple splice variants. All genes are expressed in the placenta with the exception of GH1, in which expression is restricted to the pituitary. A pituitary expressed GH gene is found in non-anthropoids.