GM-CSF Regulation Of Preimplantation Embryo Development
Funder
National Health and Medical Research Council
Funding Amount
$481,320.00
Summary
Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be ov ....Treatment of infertility using IVF technology has been enormously successful. However, there are major concerns regarding the high incidence of multiple pregnancies (caused by the transfer of more than one embryo) and the potential adverse health outcome of adults conceived from this technology. Multiple pregnancies place both mother and infant at enormous risks, with increased obstetrics care, prematurity, increased neonatal care and neurological disorders such as cerebral palsy. This can be overcome simply by the transfer of a single embryo. However, patient and clinical expectations are that single embryo transfer should be achieved with little to no reduction in pregnancy rate, and currently this is not possible because our methods for culturing embryos are inadequate. Studies in animals suggest that laboratory growth of mammalian embryos can lead to small-for-gestational age babies (even when the effect of multiple births is taken into consideration). This backed by recent studies which agree that babies born from IVF are smaller than expected. This might lead to health problems in later life, as smallness at birth is associated with higher risks of cardiovascular disease and diabetes, especially as age progresses beyond 40 years. However, the oldest IVF child is currently 23 years of age. Previously we have shown that a protein growth factor, called granulocyte-macrophage colony-stimulating factor (GM-CSF), found normally in the reproductive tract, has dramatic beneficial effects on human and mouse embryos grown in the laboratory. Furthermore, we have shown in mice that embryo exposure to GM-CSF alleviates the detrimental side effects of in vitro culture on foetal growth and body structure after birth. Our research is now focussed on understanding why this protein is beneficial to embryo growth and to test if we can increase pregnancy rates and produce normal healthy infants from the transfer of single embryos treated with GM-CSF.Read moreRead less
Macrophage-regulated Tissue Remodelling In Endometrial Receptivity For Embryo Implantation And Pregnancy Success
Funder
National Health and Medical Research Council
Funding Amount
$456,779.00
Summary
Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Moreover, 1 in 6 pregnancies is affected by pre-eclampsia, low birth weight or preterm labour. Infertility and other pathologies in pregnancy often result from failure of the maternal tissues to adequately support embryo implantation and development of the placenta, leading to insufficient nutritional support of the developing fetus. We have discovered in mice that disruption in th ....Infertility and recurrent miscarriage affect 60-80 million couples globally, including 15% of couples in Australia. Moreover, 1 in 6 pregnancies is affected by pre-eclampsia, low birth weight or preterm labour. Infertility and other pathologies in pregnancy often result from failure of the maternal tissues to adequately support embryo implantation and development of the placenta, leading to insufficient nutritional support of the developing fetus. We have discovered in mice that disruption in the populations of immune cells called macrophages within the uterine endometrial lining can reduce the receptivity of the endometrum to embryo implantation, and can lead to fetal growth retardation and impaired health after birth. The purpose of this project is to delineate the precise functions of macrophages in interacting with other cells in the endometrium to facilitate attachment of the embryo, its invasion into maternal tissues, and its access to an adequate blood supply as the placenta develops during early pregnancy. We will employ state of the art experimental strategies including genetic models to deplete endometrial macrophage populations in mice, and will then study the implications for changes in endometrial tissue structure and function. Furthermore we will investigate the long term consequences of early macrophage perturbations for the fetus and neonate after birth. This study will improve our understanding of how determinants of macrophage function such as infection and inflammatory conditions, male factors, nutrition and stress can impair fertility and compromise optimal pregnancy outcome in humans.Read moreRead less
Macrophages In Developmental Programming Of Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$532,386.00
Summary
Programming of reproductive health in women begins long before sexual maturity. Development during childhood, puberty and adulthood produces a fully functional reproductive system capable of conceiving, gestating and nurturing a child. This project will investigate the role of immune cells known as macrophages in the reproductive system, and investigate how their disruption might influence developmental programming and have lifetime consequences for the reproductive health of the individual.