How mammals evolved

Major advances in the understanding of mammalian evolution have taken place over recent years. The new science of molecular phylogenetics has clarified relationships between extant orders of mammal based primarily upon comparison of nucleotide sequences of selected genes. These remain about 20 in number, and most are unchanged from the time when orders were defined by comparing bones and teeth. What the genes reveal, however, is that they can be arranged in four major groups or superorders ( Table 1 ). Mammals evolved in the Jurassic period, and early mammals lived side by side with dinosaurs. At this time, one vast land mass (Pangaea) existed. In the succeeding Cretaceous, this land mass broke up resulting in the complete separation of present-day South America and Africa. There was a radiation of mammals on each of these continents, resulting in the superorders named Xenarthra and Afrotheria, respectively. In contrast, much of the fauna we today associate with Africa continued its evolution in a northern land mass called Laurasia. When continental drift reunited Eurasia with Africa, carnivores, antelopes and primates were first able to enter the African continent.

Marsupials (Metatheria) share a common ancestor with so-called placental mammals (Eutheria). They evolved in parallel, and most extant species are found in South America and Australasia, betraying that these continents were once part of a greater entity called Gondwana. In contrast, the monotremes (i.e. echidnas and duck-billed platypus) are part of a much older radiation.

Fetal membranes

The cleidoic egg of reptiles marked a major advance in the evolution of vertebrates, because it freed land-living mammals from their dependence on water for breeding. Within the egg, the embryo could develop in a private pond, enclosed by a thin membrane, the amnion. The amniote egg has several other membranes. The chorion is just beneath the outer shell and serves as a respiratory organ. The yolk sac contains energy-rich yolk. Everything is sealed in the shell, which is leathery in reptiles and monotremes and hard in birds. It is from these membranes that the placenta is derived.

Yolk sac placentation

In many mammals, the embryo is supported first by a choriovitelline or yolk sac placenta and later by a chorioallantoic one. This applies, for example, to domesticated species such as the pig, horse and ruminants. The yolk sac placenta is supplied by the vitelline vessels and the chorioallantoic one by vessels of an allantoic sac or stalk. Some mammals, including humans, never form a yolk sac placenta. The yolk sac floats free in the exocoelom, and here it likely has an important function in early to mid-gestation. In contrast, the yolk sac placenta in many mammals, notably rodents, persists right up to term. Partial or complete inversion of the germ layers then takes place. This concept is sometimes difficult to grasp, but the essential point is that yolk sac endoderm faces the uterine lumen, forming an absorptive epithelium.

Placental shape

Placental structure shows great variation, extending from differences in gross appearance to disparities at the ultrastructural level. The chorioallantoic placenta sometimes assumes the appearance of a fluid-filled bag. In these diffuse placentae, the surface is covered with villi that interdigitate with crypts in the uterine epithelium. An example would be the domestic pig. The horse placenta is usually assigned to this category, although here the villi are gathered in tufts referred to as microcotyledons. Most ruminants, such as cattle and deer, have cotyledonary placentae. Each cotyledon resembles a small disk and develops around a preformed structure on the uterine surface called a caruncle. The number of caruncles and thus the number of cotyledons varies from 50–175 in cattle to 5–8 in deer. In the zonary type of placenta, the trophoblast is restricted to an equatorial band of tissue (there are some variations on this theme). This type of placenta is typical of carnivores, such as dogs and cats, but is also found in elephants and manatees. The human placenta comprises a single disk and all the common laboratory rodents, including rats, mice and guinea pigs, have a discoid placenta. Many monkeys have a secondary disk and thus a double discoid placenta.

Several attempts have been made to trace the evolution of placental shape and it is generally agreed that the last common ancestor of living placental mammals (a taxonomic category that excludes marsupials) had a discoid placenta.

The interhaemal barrier

As the placenta is an organ of fetal–maternal exchange, close attention has been paid to variations in the number of tissue layers separating fetal and maternal blood. A classification introduced by Grosser, but since simplified, recognizes three principal types. Their distribution between the orders of mammal is shown in Table 1 .

In the epitheliochorial type, the uterine epithelium remains intact. In principle, the interhaemal barrier then has six layers of tissue: the endothelium of the fetal capillary; fetal connective tissue; the trophoblast (chorionic epithelium); the uterine epithelium; uterine connective tissue (endometrium or decidua); and the endothelium of the maternal capillary. In practice, there are areas of extreme thinning, and connective tissue in particular may be excluded from regions of gas exchange.

In the ‘endotheliochorial’ type of placenta, the uterine epithelium has been lost, and the connective tissue thins out, bringing the endothelium of the maternal capillaries directly in contact with the trophoblast. This type of placentation is typical of carnivores but occurs in several other orders ( Table 1 ).

In a ‘haemochorial’ placenta, all the maternal tissues have been lost, including the capillary endothelium, and the maternal blood comes directly in contact with the trophoblast. This type of placenta is widespread and occurs for example in many rodents and in higher primates, including humans ( Table 1 ). The number of trophoblast layers in the interhaemal region varies, however, so that placentae may be referred to as haemomonochorial (e.g. human, guinea pig), haemodichorial (e.g. rabbit) or haemotrichorial (e.g. mouse).

The interhaemal barrier is seen as a key feature in placentation, and how it evolved has been the focus of much discussion. Several studies, based on current phylogenies of mammals derived from molecular phylogenetics, have recently been published. All agree that the epitheliochorial type of placenta was not present in the common ancestor and must have evolved twice: once in the lower primates and once in the common ancestor of even-toed ungulates, horses and pangolins. There the agreement ends. Investigators are equally divided on whether the common ancestor of placental mammals had an endotheliochorial placenta or a haemochorial one. In addition to methodological issues, the outcome of such analyses is influenced by uncertainty about the correct rooting of the mammalian tree. There was such a rapid radiation of mammals in the Cretaceous era that even sophisticated molecular techniques cannot give an unequivocal answer to the relations between the four major clades (superorders) of mammal.

Labyrinthine and villous placentae

The vascular arrangements of haemochorial placentae conform to two distinct types. In a labyrinthine placenta, trophoblastic channels containing maternal blood run parallel to the fetal capillaries. Usually fetal and maternal blood flows in opposite directions allowing countercurrent exchange. This gives maximum efficiency when exchange is flow limited as it is for respiratory gases. A villous placenta is best understood by reference to the human placenta. Here, the fetal structures grow down from the chorionic plate as villous trees where the outer leaves are the terminal villi. Maternal blood enters from arteries in the basal plate and circulates through the intervillous space. Intermediates between the labyrinthine and villous types occur, for example, in New World monkeys and colugos.

Endotheliochorial placentae tend to be of the labyrinthine type, but most epitheliochorial placentae are referred to as villous. Nevertheless, as there is no intervillous space, they are different from the type found in primates. In these diffuse placentae, villi on the fetal surface interdigitate with crypts in the uterine wall. Branching of the villi can become quite complex in cotyledonary placentae.

It is generally agreed that the labyrinthine arrangement was present in the common ancestor of living placental mammals. To summarize, this hypothetical ancestor had a discoid, labyrinthine placenta with an interhaemal barrier that was either endotheliochorial or haemochorial. Either of the latter alternatives would imply that it was an invasive placenta.

Fetal membranes

The cleidoic egg of reptiles marked a major advance in the evolution of vertebrates, because it freed land-living mammals from their dependence on water for breeding. Within the egg, the embryo could develop in a private pond, enclosed by a thin membrane, the amnion. The amniote egg has several other membranes. The chorion is just beneath the outer shell and serves as a respiratory organ. The yolk sac contains energy-rich yolk. Everything is sealed in the shell, which is leathery in reptiles and monotremes and hard in birds. It is from these membranes that the placenta is derived.

Yolk sac placentation

In many mammals, the embryo is supported first by a choriovitelline or yolk sac placenta and later by a chorioallantoic one. This applies, for example, to domesticated species such as the pig, horse and ruminants. The yolk sac placenta is supplied by the vitelline vessels and the chorioallantoic one by vessels of an allantoic sac or stalk. Some mammals, including humans, never form a yolk sac placenta. The yolk sac floats free in the exocoelom, and here it likely has an important function in early to mid-gestation. In contrast, the yolk sac placenta in many mammals, notably rodents, persists right up to term. Partial or complete inversion of the germ layers then takes place. This concept is sometimes difficult to grasp, but the essential point is that yolk sac endoderm faces the uterine lumen, forming an absorptive epithelium.

Placental shape

Placental structure shows great variation, extending from differences in gross appearance to disparities at the ultrastructural level. The chorioallantoic placenta sometimes assumes the appearance of a fluid-filled bag. In these diffuse placentae, the surface is covered with villi that interdigitate with crypts in the uterine epithelium. An example would be the domestic pig. The horse placenta is usually assigned to this category, although here the villi are gathered in tufts referred to as microcotyledons. Most ruminants, such as cattle and deer, have cotyledonary placentae. Each cotyledon resembles a small disk and develops around a preformed structure on the uterine surface called a caruncle. The number of caruncles and thus the number of cotyledons varies from 50–175 in cattle to 5–8 in deer. In the zonary type of placenta, the trophoblast is restricted to an equatorial band of tissue (there are some variations on this theme). This type of placenta is typical of carnivores, such as dogs and cats, but is also found in elephants and manatees. The human placenta comprises a single disk and all the common laboratory rodents, including rats, mice and guinea pigs, have a discoid placenta. Many monkeys have a secondary disk and thus a double discoid placenta.

Several attempts have been made to trace the evolution of placental shape and it is generally agreed that the last common ancestor of living placental mammals (a taxonomic category that excludes marsupials) had a discoid placenta.

The interhaemal barrier

As the placenta is an organ of fetal–maternal exchange, close attention has been paid to variations in the number of tissue layers separating fetal and maternal blood. A classification introduced by Grosser, but since simplified, recognizes three principal types. Their distribution between the orders of mammal is shown in Table 1 .

In the epitheliochorial type, the uterine epithelium remains intact. In principle, the interhaemal barrier then has six layers of tissue: the endothelium of the fetal capillary; fetal connective tissue; the trophoblast (chorionic epithelium); the uterine epithelium; uterine connective tissue (endometrium or decidua); and the endothelium of the maternal capillary. In practice, there are areas of extreme thinning, and connective tissue in particular may be excluded from regions of gas exchange.

In the ‘endotheliochorial’ type of placenta, the uterine epithelium has been lost, and the connective tissue thins out, bringing the endothelium of the maternal capillaries directly in contact with the trophoblast. This type of placentation is typical of carnivores but occurs in several other orders ( Table 1 ).

In a ‘haemochorial’ placenta, all the maternal tissues have been lost, including the capillary endothelium, and the maternal blood comes directly in contact with the trophoblast. This type of placenta is widespread and occurs for example in many rodents and in higher primates, including humans ( Table 1 ). The number of trophoblast layers in the interhaemal region varies, however, so that placentae may be referred to as haemomonochorial (e.g. human, guinea pig), haemodichorial (e.g. rabbit) or haemotrichorial (e.g. mouse).

The interhaemal barrier is seen as a key feature in placentation, and how it evolved has been the focus of much discussion. Several studies, based on current phylogenies of mammals derived from molecular phylogenetics, have recently been published. All agree that the epitheliochorial type of placenta was not present in the common ancestor and must have evolved twice: once in the lower primates and once in the common ancestor of even-toed ungulates, horses and pangolins. There the agreement ends. Investigators are equally divided on whether the common ancestor of placental mammals had an endotheliochorial placenta or a haemochorial one. In addition to methodological issues, the outcome of such analyses is influenced by uncertainty about the correct rooting of the mammalian tree. There was such a rapid radiation of mammals in the Cretaceous era that even sophisticated molecular techniques cannot give an unequivocal answer to the relations between the four major clades (superorders) of mammal.

Labyrinthine and villous placentae

The vascular arrangements of haemochorial placentae conform to two distinct types. In a labyrinthine placenta, trophoblastic channels containing maternal blood run parallel to the fetal capillaries. Usually fetal and maternal blood flows in opposite directions allowing countercurrent exchange. This gives maximum efficiency when exchange is flow limited as it is for respiratory gases. A villous placenta is best understood by reference to the human placenta. Here, the fetal structures grow down from the chorionic plate as villous trees where the outer leaves are the terminal villi. Maternal blood enters from arteries in the basal plate and circulates through the intervillous space. Intermediates between the labyrinthine and villous types occur, for example, in New World monkeys and colugos.

Endotheliochorial placentae tend to be of the labyrinthine type, but most epitheliochorial placentae are referred to as villous. Nevertheless, as there is no intervillous space, they are different from the type found in primates. In these diffuse placentae, villi on the fetal surface interdigitate with crypts in the uterine wall. Branching of the villi can become quite complex in cotyledonary placentae.

It is generally agreed that the labyrinthine arrangement was present in the common ancestor of living placental mammals. To summarize, this hypothetical ancestor had a discoid, labyrinthine placenta with an interhaemal barrier that was either endotheliochorial or haemochorial. Either of the latter alternatives would imply that it was an invasive placenta.