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
The Formation And Development Of The Ovarian Follicular Membrana Granulosa
Funder
National Health and Medical Research Council
Funding Amount
$351,575.00
Summary
In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicle ....In order for the ovary to be able to release eggs and produce hormones such as oestrogen, follicles must grow within the ovary. Each follicle contains one egg and when the follicle is large and filled with fluid it can rupture, releasing the fluid and egg in the process of ovulation. A key part of the structure of the follicle is a non-cellular layer called the basal lamina. This basal lamina encapsulates the inner cells, the egg and the fluid in the follicle. Each women has millions of follicles prior to her birth, ten of thousands in her reproductive years, and none at the menopause. Since she only ovulates about 500 in her lifetime most follicles die in the process of growing to ovulatory size. This project will examine the structure of the follicle wall and the cells that make up that wall. How these cells replicate during follicle growth has never been discovered. This research has important implications for the many women who have polycystic ovarian disease, whose follicles fail to grow to full size. We will be examining these ovaries directly. The research also has importance in the next phase of IVF developments.Read moreRead less
This project aims to study how the two main hormones, FSH and testosterone, control the development and production of sperm throughout adult life. In previous NHMRC-supported research we were the first to overturn the long-standing belief that FSH was vital to the start of sperm production in all warm-blooded animals. This insight was achieved from experiments using a genetically modified strain of mouse. We used this mouse strain to develop a new experimental paradigm to provide unique insight ....This project aims to study how the two main hormones, FSH and testosterone, control the development and production of sperm throughout adult life. In previous NHMRC-supported research we were the first to overturn the long-standing belief that FSH was vital to the start of sperm production in all warm-blooded animals. This insight was achieved from experiments using a genetically modified strain of mouse. We used this mouse strain to develop a new experimental paradigm to provide unique insight into how hormones start up and support sperm production. In this present proposal we wish to take this research further. Although we have shown that FSH is not vital to the startup or continuing of sperm production, we believe it still does have an important role in causing the growth of a large enough population of Sertoli cells of the testis. These highly specialised cells have the unique job to support, nourish and coordinate the production of sperm. Sertoli cells are known to be the only target in the body for FSH and so that FSH must act upon them exclusively. We believe this occurs almost solely during early life - starting before birth and into early infancy - well before adult life when sperm are produced for the first time. In this way these processes being studied determine the size of mature testis. Our new approaches to studying the question of how the two main hormones control sperm production involve developing new types of genetically modified mice which have extra and exclusive FSH activity as well as some new research methods to be applied to understanding how FSH acts on the Sertoli cell using techniques derived from gene therapy and from cell transplantation. This research has the possibility to uncover new causes of previously unexplained male infertility (the majority having no known cause so far), to help develop better hormonal male contraceptives, and to quetion the need for expensive treatments for some infertile men.Read moreRead less