The John Hughes Memorial Lecture: Stimulation of Early Placental Development Through a Trophoblast-Endometrial Dialog

In all eutherian mammals, there are two modes for supplying nutrients to the conceptus, histotrophic and hemotrophic nutrition. In general, these modes are sequential; although in some species, the two operate in parallel throughout the entire pregnancy. Although hemotrophic nutrition is the most important for proper growth of the fetus as assessed by birth weight, there is growing evidence that the phase of histotrophic nutrition is critical for initial development of the placenta. Evidence from animal species has revealed the existence of a signaling dialog between the trophoblast of the placenta and the endometrial glands, whereby the secretion of nutrients, collectively known as uterine milk proteins, and growth factors is upregulated during early pregnancy. In this way, the placenta is able to stimulate its own development. Circumstantial evidence suggests that an equivalent dialog occurs in the human and that deficiencies in endometrial function in early pregnancy may underpin complications of later pregnancy. The conservation of the trophoblast-endometrial dialog across species, with such differences in placental types as the horse and the human, suggests that it is of fundamental importance in placentation. The implication is that attempts should be made to ensure the endometrium is in optimal condition before conception.