Uterine NKCs Play Key Role in Miscarriage Risk: Study
Suffering a miscarriage can be a very distressing experience but for many women their next pregnancy is a normal one. For women, however, who suffer recurrent miscarriage, where they have three or more in a row, it can be utterly devastating.
Although it has long been known that the lining of the womb harbours dynamic uterine natural killer cells, no functions have so far been given to these cells outside of pregnancy.
Despite their name, NK cells actually play a beneficial role in the development of an embryo. But abnormally high levels of NK cells are found in the uterus of some women (around a sixth) who recurrently miscarry. NK cells are a key player in the innate immune system, which can be triggered to defend the body from infection. One theory is that in some cases they may stop an embryo implanting in the womb. However, little is known about this mechanism.
Now, a new study by resea
rchers at the University of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust has discovered the role that Natural Killer Cells play in preparing the womb for pregnancy.
The new study Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium shows two functions of the cells not previously known. First the researchers discovered that the uterine natural killer cells remodel and refresh the lining of the womb at the time of embryo implantation. This is the first time a role for uterine natural killer cells in the lining of the womb has been identified outside of pregnancy. In addition they discovered that this process isn’t always balanced in each cycle.
“A good analogy is Swiss cheese: without holes, the embryo has nowhere to go which will cause implantation failure; but if the holes are too large, the tissue will physically collapse and lead to miscarriage,” explains lead author Jan Brosens, a professor based at the Division of Biomedical Sciences of Warwick Medical School.
This imbalance, which may be short-lived or last for multiple cycles, explains the high rate of early pregnancy failure, yet high cumulative live-birth rate that characterizes human reproduction.
“Patients suffering recurrent IVF failures or miscarriages, as well as their treating doctors, often refer to this phenomenon as the ‘numbers game,‘” adds Brosens.
In the course of their study, the researchers analyzed 2,111 endometrial biopsies and examined the acutely stressed (acutely senescent) cells in the lining of the womb which generate tissue inflammation that is needed for embryo implantation.
On observation found that the natural killer cells which are in the womb perform the important function of selectively targeting and eliminating acutely stressed cells. They perform this as the cycle progresses. Also the researchers data suggest that acutely stressed cells in the lining of the womb are responsible for generating the elusive ‘implantation signal’ in the human uterus.
Prof. Brosens added: “We hope in the future this new information will be used to screen women at risk of reproductive failure. Furthermore, our findings suggest new treatment options for women suffering recurrent miscarriages or recurrent IVF failure.”
