Department of Anatomy; University of Cambridge
Conceptuses with paternal uniparental disomy for chromosome 12 (pUPD12) have placentomegaly and fetuses die between e16.5 of gestation and term (1). In pUPD12 placenta, the labyrinthine trophoblast exhibits morphological defects affecting the structural integrity of feto-maternal interfaces in that placental zone. In addition, pUPD12 placenta have defective behaviour of glycogen cells, a population of cells found in the junctional spongiotrophoblast layer that normally migrate into the maternal decidua basalis and surround the maternal artery and veins in that zone (2). In normal placenta, this migration to the maternal spiral artery is associated with a physiological transformation of the artery. In pUPD12 placenta, the migration of glycogen cells is shallow or delayed and the artery fails to undergo its physiological transformation (3). These placental defects are reminiscent of those observed in the human pre-eclamptic placenta.
Our studies include two approaches to investigate the role of imprinted genes on chromosome 12 in these placental defects. In the first, we have investigated the extent to which the defects in the labyrinth zone are a secondary effect of a stressed placenta. This has been conducted using markers for oxidative stress and hypoxia. In the second we have characterized the expression of known and candidate imprinted genes in the placenta to determine the extent to which the defects may be a direct consequence of the altered dosage of imprinted genes in UPD12 placenta. The results of these studies will be presented.
Georgiades, P., Watkins M., Surani, M.A., and Ferguson-Smith, A.C. Parental origin specific developmental defects in mice with uniparental disomy for chromosome 12. Development, 127: 4719-4728, 2000.
Georgiades, P., Ferguson-Smith, A., and Burton, G. Comparative developmental anatomy of the definitive murine and human placenta. Placenta 23: 3-19, 2002.
Georgiades, P., Watkins, M., Burton, G., and Ferguson-Smith, A.C. Roles for genomic imprinting and the zygotic genome in placental development. Proc. Natl. Acad Sci (USA) 98: 4522-4527, 2001.