The trial objective was to determine the peripheral blood NK cells cytotoxic activity effect on trophoblast cells at recurrent pregnancy loss (RPL). The investigation involved non-pregnant women with PRL in proliferating and secretory menstrual cycle phases (PMCPh and SMCPh, respectively); women of 6-7 weeks pregnancy with RPL in past medical history; healthy fertile non-pregnant women in PMCPh and SMCPh, women of 6-7 weeks physiological pregnancy, nulliparity healthy women with regular menstrual function in PMCPh and SMCPh. NK cells cytotoxic activity was determined using peripheral blood mononuclear cells. The target cells were JEG-3 line trophoblasts. It has been established that NK cells cytotoxic activity effect on trophoblasts is lower in SMCPh than in PMCPh in non-pregnant fertile women. The NK cells cytotoxic activity was higher in SMCPh than in PMCPh in non-pregnant women with PRL and also higher than the same value in SMCPh in non-pregnant fertile women. The increased NK cells cytotoxic activity values in SMCPh in women with RPL may be the reason for miscarriage.
Background::
Maternal natural killer cells (NK cells) are a prevailing leukocyte
population in the uteroplacental bed. Current descriptions of the effect of cytokines from
the placental microenvironment on the expression of receptors by trophoblast and NK
cells are inadequate and contradictory. There is insufficient information about the ability
of NK cells to migrate through trophoblast cells.
Objective::
To assess the impact of conditioned media obtained during culturing of
placentas from the first and the third trimesters of healthy pregnancies on the phenotype
of trophoblast and NK cells and impact on adhesion and transmigration of NK cells
through trophoblast cell layer.
Results::
We established that conditioned media obtained from both first and third
trimester placentas increased the intensity of CD106, CD49e, CD49a, CD31, CD51/61,
and integrin β6 expression by trophoblast cells. Conditioned media obtained from first
trimester placentas increased the intensity of CD11a, CD29, CD49d, CD58, CD29
expression by NK cells. The presence of conditioned media from third trimester
placentas resulted in more intense CD29, CD49d, CD11a, CD29, CD49d, and CD58
expression by NK cells. Migration of NK cells through trophoblast cells in the presence
of conditioned media from first trimester placentas was increased compared with the
migration level in the presence of conditioned media from third trimester placentas. This
may be associated with increased expression of CD18 by NK cells.
Conclusion::
First trimester placental secretory products increase adhesion receptor
expression by both trophoblast and NK cells. Under these conditions, trophoblast is
capable of ensuring NK cell adhesion and transmigration.
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