Endometrial Characterisation in Women at Risk of Placental Dysfunction
Research type
Research Study
Full title
Characterisation of the Endometrium in Women at High Risk of Placental Dysfunction in Pregnancy
IRAS ID
294303
Contact name
Jenny Myers
Contact email
Sponsor organisation
University of Manchester
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Summary of Research
Background: Pre-eclampsia is a common disorder of pregnancy, affecting 4-8% of women. It is diagnosed by high blood pressure and protein in the urine. Severe cases can be life threatening, and risk long-term disease for both the mother and baby. The development of pre-eclampsia is only partially understood, but is attributed to abnormal development of the placenta that starts in early pregnancy. Successful development of the placenta relies upon cells of the embryo invading lining of the womb, known as the endometrium, that undergoes changes in preparation for implantation. Altered functioning of the endometrium could lead to poor development of the placenta, therefore leading to pre-eclampsia.Aim: To determine differences in gene expression of the lining of the womb at the time of embryo implantation, in women affected by pre-eclampsia in comparison to a low-risk control group. To explore the use of gene sequencing technology to identify altered gene expression in these samples.
Method: Women who have had pre-eclampsia will be invited to join the study. At a single research clinic appointment a medical history will be taken from the patient and endometrial sampling will be performed. Samples from these women will be compared to women who are low risk in developing pre-eclampsia. Laboratory studies will investigate for genetic differences between these women.
How it will benefit: Genetic analysis prior to the suspected time of implantation has not been performed previously. Identifying genetic differences of the lining of the womb could help us to understand the development of this disease, and may provide insight into the association of disease recurrence and pattern of maternal inheritance.
Significance of the research: The impact of severe pre-eclampsia on affected women and their babies is immense. Improving our understanding of the disease is fundamental to improve diagnosis, guide therapeutic targets and counsel affected women.
Summary of Results
Pre-eclampsia is a serious complication of pregnancy that affects the health of both the mother and baby. It is thought to arise when the placenta does not develop properly in early pregnancy. This process depends on the lining of the womb (endometrium) undergoing changes that allows the placenta to grow, and blood vessels to change to the needs of the pregnancy. Although pre-eclampsia is widely believed to start later in pregnancy, this research explored whether signs might already be present before a woman even becomes pregnant.This study investigated the lining of the womb and blood samples of women who experienced pre-eclampsia early in previous pregnancies and compared these to women without this history. The types and behaviours of cells in the lining of the womb were analysed, including stromal cells, which change to prepare for pregnancy, and different types of immune cells. Hormone levels and inflammation markers in the blood were also tested.
The findings revealed that even before pregnancy, the lining of the womb from women at risk of pre-eclampsia functioned differently. Stromal cells showed changes that can affect nearby immune cells, and showed signs that they may not prepare the womb properly for pregnancy. Differences were seen in the numbers of immune cells (macrophages) that were also not functioning as expected. Blood tests showed increased levels of inflammation and lower levels of progesterone, a hormone essential for preparing the womb for pregnancy.
These findings show that women who have had pre-eclampsia early in a previous pregnancy may already have changes in the lining of the womb and immune system before becoming pregnant again. These changes might make it harder for the womb to support a healthy pregnancy. By understanding these differences, new treatments could be given to prepare the lining of the womb better for pregnancy, and help to reduce the chance of pre-eclampsia in future pregnancies.
REC name
North West - Preston Research Ethics Committee
REC reference
21/NW/0195
Date of REC Opinion
5 Aug 2021
REC opinion
Further Information Favourable Opinion