9. T Regulatory Cells in Normal Pregnancy and Recurrent Miscarriage
Miscarriage is the most common complication of pregnancy.
T Regulatory Cells in Normal Pregnancy and Recurrent Miscarriage
Miscarriage is the most common complication of pregnancy. In fact, around one in four pregnancies will end in a miscarriage, the majority of which happen in the first 12 weeks. Around 2% of couples trying to conceive will suffer from recurrent miscarriage. This is defined as three or more consecutive pregnancy losses. In over half of patients suffering from recurrent miscarriages no underlying cause is found . Not only does recurrent miscarriage cause significant psychological morbidity but it has been shown to be associated with long-term cardiovascular risk. Immunological factors are thought to account for a significant proportion of unexplained recurrent miscarriages, although there is no consensus and much controversy as to which specific cells or immune factors are responsible.
In the very first days of pregnancy when the embryo implants into the endometrium, the maternal immune system is carefully controlled by a host of embryo and endometrium derived factors. Murine models implicate T Regulatory (Treg) cells as critical endometrial components that provide localized modulation of immune responses, essential for pregnancy success. There is evidence that there is a reduced level of FoxP3, the transcription factor that controls Treg function, in the endometrium of women who have recurrent miscarriage (3). We hypothesize that for women who suffer unexplained recurrent miscarriage a woman’s endometrial Treg are unable to provide appropriate modulation. This project will study Treg cells in the endometrium and peripheral blood of women who have recurrent miscarriage.
Research Plan: Endometrial biopsies are taken during the ‘window of implantation’ (between 7-10 days after ovulation) from women who have had recurrent miscarriage and from women who have no known fertility or miscarriage problem. Ethical approval for this study has been obtained.
This project uses both cellular and molecular immunological techniques, the student will become an expert in multiparameter flow cytometry and develop and use a broad range of immunoassays and RNASeq-based gene expression analysis.
Research training, e.g. in experimental design, data interpretation, statistical analysis and presentation and writing skills will also be provided. The department holds regular departmental seminars and journal clubs which the student will be expected to attend and they will present at both during the studentship. They will also have the opportunity to attend and present their data and national and international meetings.