Do sperm-derived factors activate endometrial NK cells? The potential role of paternal sperm derived white blood cells and soluble factors in activating non-pregnant endometrial NK cells
What is the purpose of this study?
The successful outcome of a pregnancy requires, amongst other things, that the placenta grows well so that it can supply the developing foetus. If placental growth is insufficient this can lead to a number of problems, for example babies that are small when born (intrauterine growth retardation) or high blood pressure and kidney problems in the mother (pre-eclampsia). The reason(s) why the placenta fails to develop in some pregnant women are poorly understood. However, recently it has been shown that certain cells in the pregnant womb, so called uterine NK cells, produce chemicals that help the development of blood vessels in the placenta. These uterine NK cells are present in very large numbers in the womb during a healthy pregnancy. However, we don’t know where these cells come from.
In the non-pregnant womb there is an accumulation of another type of NK cell, called the endometrial NK cell. While somewhat similar to the cells seen in pregnancy these endometrial NK cells do not support the development of the placental blood vessels. One theory suggests that these endometrial NK cells receive a “signal” during the very early stages of the pregnancy, and this changes them to uterine NK cells. While this is possible the nature of the “signal” initiating this shift is not known.
During sexual intercourse apart from the sperm, which is necessary for the fertilization of the egg, a number of the male partner’s white blood cells and various chemicals also enter the womb. This study aims to find out if either the white blood cells or some of the chemicals present in the sperm could turn endometrial NK cells to uterine NK cells.
Women having laparoscopic sterilisation to provide a permanent method of contraception. Given that they have already had children, they have proved that the lining of their womb can support a pregnancy, and hence the lining would be deemed normal. We would therefore like to take a small sample of the cells from the lining of the womb whilst they are being sterilised, so that we can use it in this research project. We hope that by looking at the cells in a normal healthy fertile population, that we will be able to make comparisons between healthy fertile women and infertile women, and hence may be able to help women experiencing infertility to get pregnant in the future.
Do they have to take part?
Participation is entirely voluntary.
What will happen if they take part?
Endometrial NK cells, taken from non-pregnant womb will be mixed with white blood cells or chemicals derived from the sperm of an anonymous donor in a laboratory. Scientists will check if any of the cells or chemicals changes the appearance or behaviour of fertile women’s endometrial NK cells that could indicate that they became uterine NK cells during the experiment. It is important to note that no embryos or stem cells can be generated during these experiments. The endometrial NK cells can only survive for a very short period outside the body and will be discarded at the end of the observation period.
What do women have to do?
During the sterilisation, it will be necessary to visualise the neck of the womb (the cervix), and an instrument will be inserted into the neck of the womb to enable us to move the womb slightly to access the fallopian tubes more easily from above. At this stage of the procedure we would like to insert a fine biopsy sampler through the neck of the womb to allow us to sample the cells from the lining if the womb. It is a little like having a cervical smear taken. This will be done whilst women are under anaesthetic and will take no longer than a couple of minutes.
What are the side effects of taking part?
Women will not experience any pain. There is a very small chance that there will be a small amount of bleeding afterwards, it will be minimal and will resolve in a day or two. While they may experience some complications as a result of their original operation participating in this study will not, in any way, contribute to these.
What are the benefits of taking part?
By taking part women will allow us to establish whether the presence of male white blood cells or chemicals in the sperm has an effect on endometrial NK cells. If such an effect can be shown, it may help us to improve the treatment of women experiencing various problems during their pregnancies in the long run. This however, is a long term goal that will require the participation of hundreds of couples in the future. There is no direct benefit to women in taking part.
What happens if something goes wrong?
As mentioned before, any problems patients may experience will be related to the treatment they are going under originally and not to the fact that we are removing cells from the uterus. Regardless of this, if they wish to complain about any aspect of the way they may have been approached or treated during the course of this study, the normal National Health Service complaints mechanisms should be available to them.
What will happen to the results of the research study?
The results will be published in international research journals. At this point only statistical data will be presented. There will be no way that any patient could be identified as an individual. Also the findings will be used in applications for further research funding.
Who is organising and funding the research?
The study is being organised by Liverpool Women’s NHS Foundation Trust and the University of Liverpool.
Who has reviewed the study?
The study has received favourable ethical approval from an independent Research Ethics Committee.