Oral Presentation 6th Australian Health and Medical Research Congress 2012

Models to study different aspects of trophoblast biology in the early human placenta.  (#77)

Larry Chamley 1 , J Prossler 1 , JL James 1
  1. Department of Obstetrics and Gynaecology, University of Auckland, Auckland, , New Zealand

The placenta is the link between mother and babe. A functional placenta is pivotal to development of the fetus in utero and the life-long health of the offspring. The human placenta implants into the uterus and placental cells, called trophoblasts, invade deeply into the uterine spiral arteries transforming them to provide a large, continuous blood supply to the placenta. Failure of implantation is a likely cause of pathologically small babies and the hypertensive disease of pregnancy, preeclampsia. Multiple functionally separate trophoblast populations arise from the outer, trophectoderm, layer of the blastocyst. However, the relationship of these trophoblast populations to each other is not clear. One of the most fundamental unanswered questions of trophoblast biology is “does the human placenta contain a trophoblast stem cell population that can differentiate into all trophoblast populations”? We have begun the search for such a human trophoblast stem cell population which might be used to answer many questions regarding the relationship between different human trophoblast populations. However, trophoblasts are only one component of the placenta and studying them in isolation may not give a true representation of trophoblast behaviour in vivo. We have developed a high-throughput model to study the responses of extravillous trophoblasts and their progenitors to various stimuli by culturing villous explants on a thin layer of Matrigel™. Extravillous trophoblasts grow out of the anchoring villi producing a quantifiable two-dimensional outgrowth that morphologically resembles extravillous trophoblast columns in vivo. We have used 1795 explants in this model to examine the effects of TGFb-1-2-3 on trophoblast outgrowth. Contrary to previous smaller studies, our results demonstrated that TGFb-2 significantly reduced the size of extravillous trophoblast outgrowths while TGFb-1 and TGFb-3 had no significant effect on extravillous trophoblast outgrowth. When studying the development of the placenta we believe it is important to choose the right model to fit the question being addressed. Our villous explant model has the advantages of being both high-throughput and quantitative.