Dr Elisabete Silva
Divisional Lead / Senior Lecturer In Human Toxicology
PhD projects for research students
Development of an in vitro 3D tissue culture model to study the effects of environmental contaminants on the human fetal-placental unit
Endocrine disrupting chemicals (EDCs) are environmental chemicals that interfere with physiological systems, adversely affecting hormone balance (endocrine system) and disrupting the normal function of organs heavily regulated by hormones, such as those of the female reproductive system. They include a variety of classes of chemicals, such as industrial by-products, pesticides and plasticisers. A common chemicals detected in human tissues is xenoestrogen bisphenol A (BPA), a plasticiser. BPA is present at levels that are 5-fold higher in the amniotic fluid than the maternal sera, due to its active transport across the placenta. Also, there is a positive correlation between BPA and miscarriages, and a link with the onset of preeclampsia; a leading cause of maternal and perinatal morbidity and mortality. Exposure to EDCs play a critical role not only in placentation but also in embryonic development and can impact later on in adult life.
Here, we propose the use of inter-connecting chambers 3D placental/umbilical cord/fetal cell models as platform to study how EDCs. Therefore, during the 3-year PhD studentship we will:
Aim 1: Establish and validate a 3D in vitro model to study fetal-placental function. We will grow commercially available placental, umbilical cord and fetal cells on a 3D matrix of inter-connecting chambers.
Aim 2: Study the effects of EDCs (e.g. BPA) using tanscriptomics and proteomics. Following treatments, we will investigate changes in the entire genome and proteome of these cells.
Aim 3: Ases the best biomarkers in terms of specificity and specificity for endocrine disruption in the feto-placental model. Using a combination of proteomic and transcriptomic arrays the most predictive biomarkers will be identified for EDCs.
All techniques are well established, so no caveats are anticipated.