Investigating how the immune system helps the placenta to implant
Research institutes:
Department of Metabolism,
Digestion and Reproduction,
Chelsea and Westminster Hospital Campus,
Imperial College LondonProject dates:
Grant Awarded: 25 Nov 2022
Funding awarded:
Grant Amount (Borne’s share): £139,512.60
Total Award: £279,024.60
Pregnancy starts with the placenta implanting itself into the lining of the womb. But problems with this process can lead to preterm birth, as well as other issues such as miscarriage and pre-eclampsia. Dr Shreya Sheth is investigating how special cells of the immune system help the placenta to implant, and what might be going wrong with these cells in pregnancies which end in preterm labour. This could lead to interventions which help save babies’ lives.
The challenge
For the early embryo to grow into a baby, it must implant its placenta into the lining of the womb. If the placenta does not implant correctly, it can lead to preterm labour, or other problems such as miscarriage, pre-eclampsia, and growth restriction.
Altogether, conditions linked to problems with placental implantation affect about 15 million babies every year worldwide, with 1 million babies tragically dying as a result.
We need to better understand what helps the placenta to implant into the lining of the womb, and why this sometimes goes wrong, so that we can save babies’ lives.
The project
The immune system is made of many different types of cells, and one group called natural killer cells (NK cells) helps protect the body from infections. Scientists have recently found special NK cells in the womb that may have an important role to play in placental implantation.
What we don’t know is exactly how these uterine NK cells (uNK cells) help the placenta to implant. We also don’t know whether something goes wrong with these uNK cells in pregnancies which end in preterm labour.
Dr Shreya Sheth hopes to answer these questions by studying uNK cells from womb samples. The samples are being donated by women who have had problems getting pregnant by IVF, and those who have had multiple miscarriages. These samples are being compared to ‘normal’ womb samples, donated by women who are having a contraceptive coil fitted.
There are three different types of uNK cells present in the womb, and Dr Sheth is measuring the amounts of the different types in the samples. She is conducting experiments in the lab which aim to simulate placental implantation, allowing her to study the behaviour of cells from women with recurrent pregnancy losses. She is also investigating what different proteins these cells produce, to understand how important these proteins are in supporting placental implantation.
What difference will this project make?
We need to understand how the placenta implants itself into the lining of the womb, and what can go wrong with this process. In this project, Dr Shreya Sheth is identifying which of the three different types of uNK cells aren’t working properly when the placenta doesn’t implant correctly. She is also identifying which molecules produced by these uNK cells are most important in this process.
By identifying opportunities to improve placental implantation, this project could eventually help reduce the number of pregnancies which end in preterm labour or other problems – helping to save babies’ lives.
This [project] will be an essential first step in developing diagnostic tools to identify women who are likely to suffer from disorders of pregnancy caused by insufficient implantation, and perhaps even promoting interventions that can promote placental implantation, ultimately reducing the burden of preterm birth associated with insufficient implantation.
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This project is a Clinical Research Training Fellowship jointly funded by Borne and the Medical Research Council (MRC)
Nurturing Talent
Dr Shreya Sheth is a doctor specialising in obstetrics and gynaecology, currently working at Chelsea & Westminster Hospital in London. During her career she has seen the many issues that women can face with pregnancy, including unexplained infertility, pregnancy loss, disorders of placental implantation, and preterm birth.
In this project, Dr Sheth is working under the supervision of Dr Viki Male, a world-leader in preterm birth research. Dr Sheth has had previous experience of lab science during her university degree at Imperial College London.
Dr Sheth’s fellowship will lead her to achieving a PhD degree, and is helping her move towards her goal of sharing her time 50-50 between clinical practice and research. She plans to use her clinical practice to translate research into tangible interventions for her patients.
This project is a Clinical Research Training Fellowship jointly funded by Borne and the Medical Research Council. Fellowships like this help medical doctors train as scientists and increase their involvement in research.
One of Borne’s key goals is to increase the number of people working in preterm birth research and improve collaboration between scientists and healthcare professionals. Clinical Research Training Fellowships, like this one awarded to Dr Sheth, help achieve this goal.
