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Endometrial-placental interactions & healthy pregnancy
Summary
Successful implantation of a human embryo into the maternal endometrium leads to a healthy placenta and a healthy baby. Impaired implantation results in inadequate placentation and can lead to miscarriage, preeclampsia and even maternal death. We aim to determine how fetal-trophoblast cells interact to invade through the maternal endometrium to form a healthy placenta.
Description
Embryo implantation involves the initial adhesion of the trophectoderm to the endometrial surface epithelium followed by the migration and invasion of the trophoblast through the maternal decidua remodelling the endometrial arteries to sequester blood to the developing placenta. These highly regulated processes are critical for pregnancy success - inadequacies in which can have far reaching consequences. Abnormalities in the very early stages of trophoblast invasion likely contribute to the development of such pregnancy complications.
Currently there is no way of determining whether the placenta is developing adequately and no effective treatment for diseases such as preeclampsia.
This project will both identify new molecules and examine the role of known molecules at the maternal-fetal interface that are critical for the development for the placenta using proteomic techniques. It will determine the function of these molecules in unique in vitro and in vivo models. It will also seek to determine whether the findings may be useful for the much needed diagnostic and therapeutic tools for major diseases associated with pregnancy.
Funding
National Health and Medical Research Council
- Contraceptive Research and Development Agency (CONRAD), USA
Outcomes
Demonstrated that interleukin 11 and leukemia inhibitory factor have critical roles in placental development.
Selected Publications
Paiva P, Menkhorst E, Salamonsen LA, Dimitriadis E (2009) Leukemia inhibitory factor and interleukin-11: critical regulators in the establishment of pregnancy. Cytokine and Growth Factor Reviews (in press)
Paiva P, Salamonsen LA, Manuelpillai U, Dimitriadis E (2009) Interleukin 11 inhibits human trophoblast invasion indicating a likely role in the decidual restraint of trophoblast invasion during placentation. Biology of Reproduction 80:302-10.
Tapia A, Salamonsen LA, Manuelpillai U, Dimitriadis E (2008) Leukemia inhibitory factor promotes human first trimester extravillous trophoblast adhesion to extracellular matrix and secretion of TIMP-1 and -2. Human Reproduction 23:1724-32
Stoikos C, Salamonsen LA, Harrison C, Dimitriadis E (2008) A distinct cohort of TGFβ superfamily members are expressed in human endometrium that regulate decidualisation. Human Reproduction, 23:1447-56.
Paiva P, Salamonsen LA, Manuelpillai U, Walker C, Tapia A, Wallace EM, Dimitriadis E. (2007) Interleukin-11 promotes migration but not proliferation of human trophoblast cells implying a role in placentation. Endocrinology 148(11):5566-72. IF=5.236
Dimitriadis E, Stoikos C, Tan Y-L, Salamonsen L (2006) IL-11 signalling components SOCS3 and STAT3 regulate human endometrial stromal cell differentiation. Endocrinology 147:3809-17.
Dimitriadis E, Stoikos C, Baca M, Fairlie WD, McCoubrie JE, Salamonsen LA. (2005) Relaxin and prostaglandin E2 regulate interleukin 11 during human endometrial stromal cell decidualization. J Clin Endocrinol Metab. 90:3458-65.
Dimitriadis E, White CA, Jones RL, Salamonsen LA (2005) Cytokines, chemokines and growth factors in endometrium related to implantation. Hum Reprod Update. 11:613-30. (cover feature)