Pre-placentation embryo support in mammals

Pre-placentation embryo support in mammals

Most biologists think that when a fertilised egg of a mammal enters the uterus it embeds in the endometrium and a placenta forms within a few days.  That is true for humans and mice, but in many (most?) species of mammal the conceptus remains free in the lumen of the uterus for some time before it attaches and placentation begins.  This is true for placental mammals such as ungulates (e.g. sheep, cattle), carnivores (dogs, cats, mustellids), and many other major groups, and also to the marsupials.  The horse shows this to a remarkable degree.  Not only does a placenta in horses not begin to form until about 35 days after fertilisation, but ithe conceptus is completely enclosed in a fibrous capsule of its own construction for the first 20 days or so.  For all of this time, the embryo grows and develops at a rate normal for  mammals.  So, how does it get fed?  The problem is the more puzzling when one considers that many of the nutrients essential to a growing and developing embryo, including delicate lipids like retinoids (vitamin A and its relatives), are not water soluble and are destroyed if not protected during transport.  We began working with Dr Francesca Stewart on a protein that her lab had discovered that is produced by the mother, crosses the capsule and enters the conceptus in large quantities.  The protein goes by the name of 'P19' or 'uterocalin', but we may be changing it to 'Equicalin'.  We found that it binds polyusaturated fatty acids and retinol, so it is most probably essential to the provisioning of the conceptus.  Retinol is a precursor for a range of signalling molecules that are known to be crucial to the proper development of an embryo.   Remarkably, the protein is also unusual in that it is enriched in essential amino acids that the embryo could not synthesise itself.  So, not only does the protein carry essential food, but it is itself comprised of essential nutrients.

We are now wondering whether proteins with similar characteristics are involved in supporting the pre-placentation conceptuses of other placental mammals, and marsupials.  Something like it might even occur in humans, in which it has recently been found that the embryo is probably also supported by secretions before full scale nutrition by a placenta begins towards the end of the first trimester.  Also, as mammals evolved from egg-layers to viviparus animals, was a protein like the one from the horse required to nourish the conceptus before placentas evolved their full modern function?

All of this, as always, was done for pure curiosity, but knowing the structure and properties of the horse protein may be useful in improving horse breeding, embryo culture, or in guarding against accidentally transporting certain drugs to the conceptus when treating pregnant mares.  We are now working with Keith Betteridge, Tony Hayes and Jim Raeside at the University of Guelph, Ontario, to look more into the biology of the protein.

Here is a picture of a horse conceptus to show how much growth and development has ocurred by about 36 days and without any direct cell-cell contact with the mother.