Immunobiology Of Early Pregnancy - A Model Of Virus-induced Abortion
Funder
National Health and Medical Research Council
Funding Amount
$454,500.00
Summary
The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft trans ....The lack of 'self' molecule expression on the trophoblast cells of the placenta which interface directly with the mother's circulation, as well as the local suppression of the mother's immune response at this interface, may be important factors in the successful implantation of the embryo. This immunological 'silence' allows the embryo, whose paternal genetic contribution makes it immunologically foreign to the mother, to escape the rejection reaction normally associated with foreign graft transplantation. Infection with flaviviruses increases the concentrations of cell surface self and adhesion molecules in vertebrate cells, including the trophoblast cells of the placenta. As a result, these molecules can then be recognised by the maternal immune system and the embryo targeted for destruction. We hypothesise that the induction of these molecules by this and other viruses may break the immunological silence of the early embryo and reverse the local suppression of the maternal immune response. This would result in maternal immune rejection of the embryo and abortion. This initial sensitisation of the mother by the virus might be one of the reasons that some women suffer recurrent abortions. We will use a novel viral mouse model where we implant virus-infected embryos into receptive animals to enable us to dissect out the unusual requirements for induction of maternal anti-viral immunity during pregnancy. This model was developed in our laboratory to directly test our hypotheses. It does not cause systemic illness in the mother which itself can lead to non-specific abortion. This model therefore can for the first time elucidate the specific mechanisms associated with the delicate balance between eradicating virus and maintaining pregnancy. Results from this project will inform rational design of treatment of recurrent abortions in the community.Read moreRead less
Neuroendocrine Mechanisms By Which Leptin Regulates Reproduction
Funder
National Health and Medical Research Council
Funding Amount
$447,750.00
Summary
The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not k ....The reproductive system is sensitive to alterations in body weight. In particular, low body weight causes the reproductive system to cease functioning. This is because the brain 'senses' metabolic status and responds by ceasing to secrete the brain hormone that drives the reproductive process. This hormone is gonadotropin releasing hormone that acts on the pituitary gland to control the release of gonadotropins. These, in turn, act on the gonads. How the brain perceives metabolic status is not known. Leptin is a hormone that is produced by fat and acts on the brain. This appears to be one of the means by which the reproductive system is regulated. Leptin also regulates food intake and other brain processes. Leptin acts on specific cell types in the brain. Some of these may have dual function to regulated appetite as well as reproduction. The present proposal is for work to determine mechanisms within the brain that are altered by leptin. We will also determine which specific mechanisms relate to the regulation of gonadotropin releasing hormone. The work will provide information on how putative appetite regulators might affect the reproductive axis. Such work will provide a platform for design of pharmaceutical means to manipulate the reproductive axis and will impact on the design of drugs that regulate obesity. It is possible that drugs that developed to control obesity may affect the reproductive axis and the project will identify these.Read moreRead less