Evolution of oxytocin and the oxytocin receptor

Evolution of vasopressin and oxytocin family of nonapeptides

From Gwee et al. (here) © 2008 Gwee et al; licensee BioMed Central Ltd.

Delivery of the fetus and placenta depends in part on the action of oxytocin (a pituitary hormone) on oxytocin receptors in the myometrium. Duplication of the vasotocin (VT) gene of lampreys was the basis for the evolution of oxytocin (OT) and arginine vasopressin (VP).

A fresh study (here) confirms this scenario but takes a closer look at the evolution of the receptors. There are three receptors for vasopressin and one for oxytocin. In essence the hypothesis is that these arose during the whole genome duplications that are thought to have occurred early in the evolution of vertebrates. It is noted that these two rounds of duplication would in theory have produced four vasotocin genes. If so, three were lost and the fourth only later gave rise to the oxytocin gene by a separate tandem duplication event. The gist of the argument is that the receptor evolved first.

Whilst oxytocin acts on the mammary glands and uterus of mammals, vasopressin acts on the kidney. In addition, both peptides act as neurotransmitters in the brain. Yamashita and Kitano suggest the neurotransmitter role came first. Only later were receptors expressed in peripheral organs such as the uterus and the peptides secreted as hormones from the posterior pituitary.

Alfred Russel Wallace

Alfred Russel Wallace from the frontispiece of Darwinism 1889 



The current issue of Nature (here) carries an appreciation of Alfred Russel Wallace, who independently of Darwin hit upon the principle of natural selection. He had a firm grasp of the species concept based on his experiences in Amazonia. In 1852 he reported on the distribution of Neotropical primates writing, "I soon found that the Amazon, the Rio Negro and the Madeira formed the limits beyond which species never passed" (On the monkeys of the Amazon Proc Zool Soc Lond 1852; 20: 107-110).

Humming-bird fertilizing Maregravia nepenthoides

from Darwinism 1889 

Wallace was based on Barra at the confluence of the Amazon and the Rio Preto. During the subsequent rubber boom it was transformed to the prosperous city of Manaus with a world class opera house. It is now home to the prestigious National Institute of Amazonian Research (INPA). Wallace's expedition, however, ended with the loss of many of his specimens in a fire on the ship that was to have carried him back to England.

The man who knew islands

Next Wallace went to Indonesia. His work there is recounted in The Malay Archipelago (1869), as reviewed in a companion article in Nature by Richard Quammen. Wallace is regarded as the father of biogeography. Quammen devoted a long chapter to him in the prize winning book Song of the Dodo (reviewed here). Among his legacy is the concept known as the Wallace Line, a water barrier that separates the Southeast Asian and Australasian flora and fauna. If you are planning a trip to Bali remember to include the Gili Isles and you will cross the Wallace Line as you go. 

To finance his travels, Wallace collected many specimens of the same species. As Quammen writes, "one effect of this redundant, commercial collecting was that he saw intraspecific variation laid out before him." This led him to the principle of natural selection, which Darwin was slow to gestate.

Giraffe placenta

Giraffes in winter quarters at Odense Zoo
Courtesy af Jonathan Thorvaldsen

Recent phylogenies (here and here) show a basal split among pecoran ruminants in the Late Oligicene, with Giraffidae (giraffe and okapi) and Antilocapridae (pronghorn) on one branch and Bovidae (cattle, sheep and goats, antelopes), Moschidae (musk ox) and Cervidae (deer) on the other. Hitherto, detailed knowlege about placentation has been limited to domesticated species from the latter group.

Delivered giraffe placenta with cotyledons from Benirschke (here)

The new study of of the maternal-fetal interface in two giraffe placentas by Sandra Wilsher and others (here) is therefore important. It confirms that the placenta is polycotyledonary and that binucleate trophoblast cells are present in fewer numbers than in sheep, cattle and deer. Binucleate cells in the placentomes stained intensely for prolactin whereas binucleate cells in the intercaruncular regions did not. This hormone might play a role in the production of accessory corpora lutea in the ovaries of the mother and the female fetus. It remains to be determined if the antibody was binding to a protein identical to pituitary prolactin or to a placental lactogen. The giraffe genome would appear to be uncharted territory.

At the edges of each placentome there were marginal folds of allantochorion situated above the openings of dilated uterine glands, suggesting a route for histiotrophic nutrition.

Resurrecting mammoth hemoglobin

Mummified baby mammoth at the Field Museum (Wikipedia Commons)

National Geographic’s cover story, “Reviving Extinct Species,” has garnered much media attention as well as serious debate (e.g. here). I was struck by the apparent assumption that an ovum with a reconstructed mammoth genome could be gestated in an elephant uterus. Experience with embryo transfer between closely related species is not encouraging. 70% of donkey-in-horse pregnancies ended in abortion after 80-85 days because of defective placental development (reference here).

Perhaps less spectacular but nonetheless impressive is the resurrection of mammoth hemoglobin achieved 3 years ago by a team led by Kevin Campbell of the University of Manitoba (here). They were able to make functional analyses that revealed adaptations for cold tolerance.

Primates and some other mammals have a fetal hemoglobin with high oxygen affinity that aids oxygen transfer across the placenta. Many mammals use a different trick to raise the oxygen affinity of fetal blood. The fetal red cells have a low content of the hemoglobin ligand DPG thereby increasing the molecule's affinity for oxygen (explained here). DPG certainly binds to mammoth DPG, raising the possibility that mammoth fetuses, too, had red cells with a low DPG content.

Mouse lemurs

Peters' mouse lemur (Microcebus myoxinus) Wikimedia Commons

Mouse lemurs are the smallest primates. Two new species have just been described bringing the total to twenty.

A previous post (here) emphasized that placentation in Malagasy lemurs is remarkably similar to that of the lorises and bush babies of Asia and Africa, i.e. diffuse in shape and epitheliochorial.

Mouse lemurs though have elaborated on this pattern. Firstly the diffuse shape is broken by a more compact disk-like portion. Secondly some areas of the placenta have become endotheliochorial through the local loss of uterine epithelium (Reng Z. Saugertierkd 1977; 42: 201.14).

Naming of the Trophoblast

Ambrosius Arnold Willem Hubrecht (Wikimedia Commons)

Robert Pijnenborg and Lisbeth Vercruysse have written an excellent paper (here) on the Dutch embryologist A. A. W. Hubrecht. He it was who coined the term trophoblast to describe cells of fetal origin with a nutritive function. 

One of Hubrecht's sections of the hedgehog placenta

Labels as in the original paper

Hubrecht applied the term to the cells in the labyrinth of the hedgehog placenta. The layer beneath that was called the trophospongium. Hubrecht mistakenly thought it was maternal in origin, but we now know it is spongiotrophoblast. There was in addition a layer of cells he called deciduofracts; these are trophoblast giant cells.

Hubrecht's collection is now curated at Museum für Naturkunde in Berlin.

Marsupial placentation

Embryo and fetal membranes of a marsupial

© 2011 Menzies et al; licensee BioMed Central Ltd.

This stunning photo of a tammar wallaby at 18 days gestation shows the vascular (TYS) and non-vascular (BYS) regions of the yolk sac. It will attach to the uterus and, as a yolk sac placenta, support fetal growth until delivery at 26-27 days. All marsupials have a yolk sac placenta. A few develop an additional chorioallantoic placenta (including the wombats).

Common wombat (Vombatus ursinus) Wikimedia Commons

Marsupials and their kin (Metatheria) share a common ancestor with “placental” mammals and their kin (Eutheria). Freyer et al. (2003) suggested that ancestor may have had both a yolk sac placenta and a chorioallantoic placenta.

As in placental mammals, the placenta of marsupials is more than an organ of maternal-fetal exchange. It is known to produce several hormones and recent studies extend the list to include growth hormone (GH), prolactin (PRL) and luteinizing hormone (LH). These hormones are expressed in the placentas of other mammals and in some elaborated as placental lactogens and chorionic gonadotropins. As argued by Menzies et al. (2011) this is further evidence of the affinity between placentas of “placental” mammals and marsupials.

Between Scylla and Charybdis

There are sound reasons for distinguishing between Placentalia and Eutheria. The former is the clade including living mammals (minus marsupials and monotremes) and their common ancestor. The latter includes extinct lineages that share a number of characters with Placentalia. Similar reasoning discriminates between Marsupialia and Metatheria.

The problem arises with the vernacular terms “placentals” or “placental mammals.” Understandably this is anathema to students of marsupial placentation. However, if “eutherians” is used to represent this group, phylogeneticists are quick to take offence.