Abstracts
Why mum must be tolerant of you . . . even before you're born
Lachlan Moldenhauer
PhD student, University of Adelaide,
Discipline of Obstetrics and Gynaecology
Supervised through Obstetrics and Gynaecology, University of Adelaide
Introduction of foreign material, such as an organ transplant, into a host usually initiates an immune response leading to rejection of the tissue. A fetus and its placenta (the conceptus) contain genes from both its mother and father. Therefore the conceptus produces father-derived molecules that are foreign to the mother’s immune system. In successful pregnancy the mother's immune system activates tolerance towards the father's foreign molecules. Thus, unlike the organ transplant, the foreign conceptus is not rejected. However, failure of the mother’s immune system to establish tolerance can result in infertility or miscarriage.
The processes leading to tolerance of the father's molecules is not well understood, but must involve these molecules interacting with cells of the mother's immune system called lymphocytes, thus inducing the lymphocytes into a tolerant state. However, it is unknown how and when male-derived molecules are presented to the mother’s immune system. The aim of this study was to determine if, when and how the father's molecules present in semen, and produced by the conceptus, can interact with lymphocytes.
To investigate this, we have developed highly sensitive and specific genetic systems that allow us to precisely measure the mother's immune responses to father-derived molecules. Using this system we have shown that the mother's lymphocytes interact with father-derived molecules in semen and father-derived molecules inherited and produced by the conceptus. This interaction induces the mother’s lymphocytes into a state of tolerance, which allows for successful pregnancy. Importantly, this knowledge will assist in designing new therapeutics to treat infertility where maternal immune problems are implicated.
