Transplacental transport of water and solutes is central to fetal growth and well-being. Despite this, the pathways and molecular mechanisms of transport and the forces driving maternal-fetal exchange are still largely unexplored. There is evidence that paracellular pathways connect the maternal intervillous space and the fetal extracellular space, but osmotic and diffusional forces acting via these pathways cannot account for the observed rates of water and solute transfer. Thus it is probable that a large fraction of w and small solute transport takes place across the cellular syncytiotrophoblast, via solubility-diffusion, channel, or carrier-mediated mechanisms. No information exists on the osmotic or diffusional permeabilities of either apical or basal syncytiotrophoblast membranes nor on the transmembrane pathways for water and solute movement. 'ne goals of this project are to define the molecular mechanisms and pathways of water and solute =sport across the syncytiotrophoblast apical and basal membranes and t identify the factors which regulate membrane permeability to water and solutes. This approach is necessary as the two syncytial surfaces are very different in both structure and function. The key elements in the proposed analyses are the use of new optical techniques for measurement of membrane transport and o recently developed syncytiotrophoblast membrane preparation. """"""""Paired"""""""" apical and basal membrane vesicle fractions will be prepared from the same placental tissue and used to measure the osmotic and diffusional permeabilities of water and the permeability coefficients for a range of solutes. The effects of solute lipophilicity and molecular volume on transport will be investigated to determine whether solute crosses apical and basal membranes by lipid, protein channel or carrier-mediated pathways. The gestational development of apical and basal permeability will be determined as a framework for exploring the relationship between membrane structure and function. Strong evidence exists to suggest significant differences in permeability between pre-term and full-term membranes. These differences will be exploited to identify the molecular factors which regulate membrane permeability; the composition and structure of pre-term apical and basal membranes will be analyzed in parallel with the measurements of water and so permeability. The analyses will include measurements of phospholipid and protein composition, membrane fluidity, lipid phase separation and lateral mobility. Ibis research will provide for the first time, quantitative information on these basic placental transport processes in the human, and their gestational development. In the longer term, this research will provide the basis for an integrated placental transport model, will aid in the analysis of transport disorders such as pre-term labor and intrauterine growth retardation and in understanding how changes in membrane composition and structure in vivo can affect transport.
| Jansson, T; Powell, T L; Illsley, N P (1999) Gestational development of water and non-electrolyte permeability of human syncytiotrophoblast plasma membranes. Placenta 20:155-60 |
| Powell, T L; Jansson, T; Illsley, N P et al. (1999) Composition and permeability of syncytiotrophoblast plasma membranes in pregnancies complicated by intrauterine growth restriction. Biochim Biophys Acta 1420:86-94 |
| Grullon, K; Jacobs, M M; Li, S X et al. (1995) Beta-adrenergic regulation of cyclic AMP synthesis in cultured human syncytiotrophoblast. Placenta 16:589-97 |
| Jansson, T; Illsley, N P (1993) Osmotic water permeabilities of human placental microvillous and basal membranes. J Membr Biol 132:147-55 |
| Jansson, T; Powell, T L; Illsley, N P (1993) Non-electrolyte solute permeabilities of human placental microvillous and basal membranes. J Physiol 468:261-74 |
| Jacobs, M M; Li, X; Illsley, N P (1992) Dual regulation of human syncytial adenylyl cyclase. Placenta 13:123-33 |
