Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Placental Slc13a4 sulphate transporter is linked to fetal abnormalities and death. (#338)

Joanna Rakoczy 1 2 , Paul Dawson 2 , David G Simmons 1
  1. School of Biomedical Sciences, University of Queensland, St. Lucia, QLD, Australia
  2. Mater Research Institute, University of Queensland, Woolloongabba, QLD, Australia

Sulphate is an important nutrient for fetal growth and development. The developing fetus is unable to generate sulphate and relies on sulphate from the maternal circulation via the placenta. In the mouse and human placenta, we identified abundant expression of the Slc26a2 and Slc13a4 sulphate transporters. Expression of Slc13a4 is restricted to the syncytiotrophblast layer in the human and to the second layer of syncytiotrophoblast (SynT-II) in mouse placenta. Slc26a2 is expressed in cytotrophoblast cells of the human placenta and the first syncytial layer (SynT-I) in mouse. Since Slc13a4 is situated in the transporting syncytia of both mouse and human placenta throughout gestation, and is not widely expressed in the fetus, we chose to further investigate its role in placental sulphate transport and fetal development by creating an Slc13a4 knockout mouse.

Slc13a4-/- placentae appear normal, whereas E14.5 and E16.5 Slc13a4-/-fetuses exhibit a multitude of developmental phenotypes including impaired development of vascular and lymphatic vessels, as well as complete loss of bone mineralisation. Importantly, all these phenotypes were rescued when we created an Slc13a4 conditional knockout mouse, which retained Slc13a4 expression in the placenta, but not in the fetus. This finding indicates that the phenotypes observed in the global knockout can be attributed to a loss of placental Slc13a4 expression. Interestingly, the severe phenotype of Slc13a4-/- embryos encompasses the phenotypes reported for individual mouse knockout models of impaired sulphonation of structural molecules important for fetal development.  The current study is providing valuable insight into the critical role of placental sulphate transport during mouse gestation, which has relevance to human SLC13A4 that shares high homology and similar tissue expression with mouse Slc13a4.