Normal pregnancy

A placenta that develops and functions adequately is essential for a healthy and successful pregnancy, as the placenta acts as the porthole through which nutrients and waste products are exchanged between the mother and the developing baby.

Consequently our Centre’s portfolio of projects on the development and function of the placenta span from the beginning of pregnancy through to late gestation with an emphasis on establishing and refining laboratory models that replicate normal placental function.

Biology of embryo implantation

Inappropriate interactions between the embryo and uterus at an early stage lead to infertility, early miscarriage or complications later in the pregnancy. Animal models have provided important clues about implantation, but the mechanisms still need to be tested in humans as they are not well enough understood to be able to diagnose and correct implantation failure.

Current projects in this area include:

  • Adhesion signalling in embryo-epithelial interactions at implantation: Aplin, Brison, Forbes, Westwood in collaboration with Kimber (Faculty of Life Sciences)
  • The role of microRNAs in regulating embryo implantation: Forbes, Aplin

How does the placenta take over the uterus?

Following implantation, cells from the early placenta migrate into the spiral arteries of the maternal uterus, transforming them into large funnel-shaped channels. This ensures that a high volume of maternal blood, containing nutrients and oxygen, are delivered to the placenta throughout pregnancy. Little is known about the mechanisms involved in remodelling these arteries.

Current projects in this area include:

  • Sphingosine-1-phosphate control of extravillous trophoblast migration: Johnstone, Westwood

Development of the placental maternal/fetal exchange barrier

In early pregnancy, the placenta develops a specialised cell layer (the syncytiotrophoblast) responsible for the production of many of the hormones of pregnancy, for protection of the fetus against attack and for maternal/fetal nutrient and waste exchange.

To remain effective, the syncytiotrophoblast must be continually renewed throughout the pregnancy. This is achieved via an orderly sequence of cell division, cell specialisation and cell death. Little is known about this vital process and how it is regulated so several of our projects are looking at this aspect of placental development.

Current projects in this area include:

  • Nutrient sensing by the placenta, which aims to identify the molecular pathways lining maternal diet to placental growth: Westwood, Aplin
  • Investigating the role of placental microRNAs: Forbes, Jones
  • Use of nanoparticles to deliver growth signals to the placenta: Aplin, Harris, Westwood in collaboration with Dr CP Case, University of Bristol

Placenta in maternal/fetal exchange of nutrients

In humans all essential nutrients for normal fetal development and growth are transferred from mother to fetus across the syncytiotrophblast - a membrane of the placenta which both protects the fetus and acts as a transporter of nutrients and waste.

Any alteration in the expression or activity of 'transporter' molecules can reduce fetal growth. Several of the Unit's projects are aimed at understanding how these important molecules are regulated.

Current projects in this area include:

  • Glucose handling by the placenta: Myers, Heazell, Westwood
  • Amino acid transport through the placenta: an experimental and modelling investigation: Glazier, Johnstone, Sibley, Crocker in collaboration with Dr Rohan Lewis, University of Southampton

Role of the placenta in protecting the fetus

The human placenta acts to protect the fetus from drugs and toxic substances (xenobiotics) present in maternal blood. In other tissues, a class of proteins called the ABC transporters has been shown to be important in protecting an organism from such compounds.

We have recently shown that one such transporter - P-glycoprotein - is produced on the maternal side of the placenta and is important in reducing the build-up of toxins in the fetus.

We have also identified small changes in the gene for this protein, which reduce its effect in placental cells. We are now investigating if these changes in the genes of other ABC transporters also cause changes which reduce the placenta's abilities to protect the fetus from exposure to toxic substances.

Fetoplacental vasculature

In normal pregnancy, the developing fetus receives nutrients from the maternal blood system via the placenta. So the control of the maternal blood supply to the placenta, and its regulation through the placental vascular tree, is important for the normal growth and development of the fetus.

Much of our attention is focused on the regulation of placental blood flow, because appreciating the molecular mechanisms controlling the flow of blood through this crucial organ is essential to the understanding of fetal growth in normal pregnancy.

Current projects in this area include: