- The role of natural killer cells in pregnancy and recurrent
miscarriages has been widely studied with often conflicting results
- Current study identifies possible link between recurrent
miscarriages and natural killer cells in the uterus lining (uNK).
Role For Natural Killer Cells In Pregnancy/Miscarriage
- Decoding the Puzzle
It has been known for long that the lining
of the uterus contains dynamically active natural killer cells but until now
their function remained a mystery.
killer cells in the uterine lining may play
a crucial role in each menstrual cycle to prepare it
to receive the implanted embryo
in case of
possible pregnancy. A defect or imbalance of this function might result in
recurrent miscarriages, according to a recent study conducted at the University
of Warwick and University Hospitals Coventry and Warwickshire (UHCW) NHS Trust.
Senescent Decidual Cells In the Womb - Novel Role of NK Cells Identified
Current study titled "Clearance of
senescent decidual cells by uterine natural killer cells in cycling human
endometrium" appears in eLife
discovered two major functions
performed by the natural killer cells in the
lining of the uterus.
- In a major breakthrough, the study
team discovered that the natural killer cells renew and remodel the
uterine lining during each menstrual cycle to make it ready to receive the
- This remodeling is achieved by
clearing the senescent and stressed decidual cells in the uterine lining
(endometrium) to create space for the embryo to be implanted.
However, this process
is not always perfect and sometimes too
many cells may be cleared,
while at other times, not enough of these cells are cleared
to make space for the embryo.
‘Excessive removal of senescent decidual cells by NK cells or too little clearance, both could result in recurrent miscarriages
Lead author Professor Jan Brosens who is
based at the Division of Biomedical Sciences Warwick Medical School said:
"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
can either be short-lived or continue over several successive cycles
explaining the reason for high degree of early pregnancy loss despite the high
overall live birth rate that is characteristic of the human race.
Endometrial Biopsies To Study The Natural Killer Cell Dynamics
Overall, 2111 endometrial biopsies
were studied that were donated by
women who attended the Implantation Research Clinic at UHCW NHS Trust. The team
looked at the senescent lining cells of the womb and the natural killer cells
in the uterine lining.
- The senescent cells of the lining of
the uterus produce inflammation, which the NK
cells target and clear
- Though this function is performed
throughout the cycle, it becomes particularly evident as the cycle
progresses, and after the ovulation in preparation of
The findings of the study seem to suggest
that the old and senescent cells lining the uterus are necessary for producing
the so called "implantation" signal in the womb.
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."
Killer Cells - An Overview
Natural killer cells
are a special type of lymphocytes (a type of white blood cell) i.e. large
granular lymphocytes and are a crucial component of the innate immune system.
They play a major 'first line of defence' role in protecting the body against
viral and bacterial infections and against growth of cancer cells.
These cells have been so named as they
have the ability to "naturally kill" or destroy invading cells (microbes) or
tumor cells without the need for any activation or priming. This is an
important property as other immune cells can only recognize invading cells that
have certain markers /antigens (eg major histocompatibility or MHC1 antigens)
on their surface.
Research on NK Cells In The Womb - Conflicting Results
In order to elucidate the possible role
of the uterine NK (uNK) cells several studies have been conducted, many of them
based on the hypothesis that NK cells might play a role in recurrent
miscarriages or pregnancy
failure in women
- A study in 1999 suggested that uterine
NK cells could cause recurrent miscarriages due to the finding of
increased uNK cells in the endometrial lining. However there was not
enough evidence to explain their findings
- A more recent study in 2007 again
found increased numbers of uNK cells, again suggesting their possible role
in recurrent miscarriages but the study failed to assess subsequent
- On the other hand, several reviews
and meta analyses have not found
any significant difference in uNK cell numbers between women with
recurrent miscarriages and normal controls. However blood levels of NK
cells was significantly higher
- Still other studies have concluded
that levels of NK cells in
peripheral blood (pNK) do not correlate or predict the numbers and/or
function of uNK cells and measuring pNK levels might thus not be
useful in predicting miscarriage or infertility
In the background of several
contradictory research outcomes, the findings of this study seem to suggest
that an appropriate degree of uNK
activation and function is necessary for successful pregnancy
. However more
studies may be necessary to further elucidate the role of senescent cells
and/or uNK cells to frame guidelines for screening and predicting miscarriage
- Natural Killer Cells And Infertility - (https://www.fxmedicine.com.au/blog-post/natural-killer-cells-and-infertility)
- Natural Killer Cells in Miscarriage and Infertility - (http://www.ivf1.com/natural-killer-cells-miscarriage-infertility/)
- The role of decidual cells in uterine hemostasis, menstruation, inflammation, adverse pregnancy outcomes and abnormal uterine bleeding - (https://www.ncbi.nlm.nih.gov/pubmed/26912000)