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
Glucose, Glucose Transporters And Blastocyst Formation In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$281,650.00
Summary
Embryo-based biotechnologies have the potential to improve human reproductive health, notably in treating infertility by In vitro fertilisation (IVF). They are also central to the future use of embryonic stem cells for human tissue replacement. This project investigates the molecular mechanisms controlling one of the earliest differentiations in the growth of the embryo. Using the mouse as an experimental model it will investigate the importance of several factors in the changes which set up the ....Embryo-based biotechnologies have the potential to improve human reproductive health, notably in treating infertility by In vitro fertilisation (IVF). They are also central to the future use of embryonic stem cells for human tissue replacement. This project investigates the molecular mechanisms controlling one of the earliest differentiations in the growth of the embryo. Using the mouse as an experimental model it will investigate the importance of several factors in the changes which set up the placenta and fetus as seperate tissues in the very early embryo. A key focus is the supply of glucose to the newly fertilised embryo and how important this glucose supply is for the survival of the embryo. Moreover there is great interest in the possibility that metabolic events in utero can contribute to the development of diseases in later life, notably, coronary heart diease, stroke, high blood pressure and non-insulin dependent diabetes. The results from these studies will contribute to our understanding of why some couples are infertile, lead to improved management of infertility by diet and invitro fertilisation procedures. It will also be of benefit in dietary advice to women with diabetes mellitus, seeking to have children. The adenoviral strategy for gene delivery into early mouse embryos may in the long term also find wide clinical application in the treatment of genetic defects at the very earliest stages in development and as such is of enormous potential benefit in the management of both animal and human reproduction.Read moreRead less