ASSOCIATIONS BETWEEN STEM CELLS AND MACROPHAGES IN THE MID-SECRETORY ENDOMETRIUM

Abstract

The human endometrial stroma contains certain stem cell types, sush as NOTCH1-positive and CD117- positive stem cells, which are essential for the periodic uterine regeneration. Besides their role in tissue remodeling, it has been proposed that they exert immunomodulatory and anti-inflammatory effect on the components of the immune system. One of the main components of the endometrial immune regulators during the mid-secretory phase of the menstrual cycle is the macrophages population. It is known that the macrophages immunoreactivity, in terms of pro- and anti-inflammatory cytokines secretion in the endometrium during the implantation window, is pivotal for the successful embryo implantation. The association of the endometrial stem cells with macrophages during mid-secretory phase of the menstrual cycle is poorly studied. The aim of this study was to find associations between the amounts of the local stem cells and macrophages in the mid-secretory endometrium of IVF patients.
Endometrial samples from 107 female IVF patients were obtained as regular diagnostic biopsy during the mid-secretory phase of the menstrual cycle (LH+7). Samples from patients with immunological or endometrial pathologies were not included. For identification of CD68+ macrophages, CD117+ stem cells and NOTCH1+ stem cells, all samples were immunohistochemically stained with the respective antibodies. Evaluation of the positively stained stromal cells was performed by microscopic observation of multiple tissue areas. Results were presented as percentage of positively stained stromal cells. Statistics: SPSS v.21.
In the mid-secretory endometrial stroma of the studied patients 0.55% (0.07-14.44%) CD68+ macrophages, 0.02% (0-0.21%) CD117+ stem cells and 0.062% (0-2.1%) NOTCH1+ stem cells were found. Spearman correlation analysis revealed low, but significant positive relation between CD68+ macrophages and CD117+ stem cells percentages (R=0.216, p=0.025), while no correlation was observed with NOTCH1+ stem cells percentage (R=0.150, p=0.123).
In conclusion, the observed correlation between CD68+ macrophages and CD117+ stem cells, and lack of relation to NOTCH+ stem cells, suggests a possible regulation of the macrophages endometrial distribution by the local CD117+ stem cells or vice versa. These findings demonstrate that there is a CD117+ stem cell to immune cell communication in the endometrial stroma that could be associated to fertility and should be further studied.

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ASSOCIATIONS BETWEEN STEM CELLS AND MACROPHAGES
IN THE MID-SECRETORY ENDOMETRIUM
RUMIANA GANEVA1,2*, DIMITAR PARVANOV1, NINA VIDOLOVA1,
MARGARITA RUSEVA1, MARIA HANDZHIYSKA1,
DIMITAR METODIEV1, VESELINA MOSKOVA-DOUMANOVA2,
GEORGI STAMENOV1
1 – Nadezhda Women’s Health Hospital, Soa, Bulgaria
2 – Department of Cell and Developmental Biology, Faculty of Biology, Soa
University “St. Kliment Ohridski”, Soa, Bulgaria
*Corresponding author: rum.ganeva@gmail.com
Keywords: endometrium, mid-secretory phase, macrophages, em cells
The human endometrial roma contains certain em cell types, sush as
NOTCH1-positive and CD117- positive em cells, which are essential for
the periodic uterine regeneration. Besides their role in tissue remodeling, it
has been proposed that they exert immunomodulatory and anti-inammatory
eect on the components of the immune syem. One of the main components
of the endometrial immune regulators during the mid-secretory phase of
the menrual cycle is the macrophages population. It is known that the
macrophages immunoreactivity, in terms of pro- and anti-inammatory
cytokines secretion in the endometrium during the implantation window,
is pivotal for the successful embryo implantation. The association of the
endometrial em cells with macrophages during mid-secretory phase of
the menrual cycle is poorly udied. The aim of this udy was to nd
associations between the amounts of the local em cells and macrophages
in the mid-secretory endometrium of IVF patients.
Endometrial samples from 107 female IVF patients were obtained as
regular diagnoic biopsy during the mid-secretory phase of the menrual
cycle (LH+7). Samples from patients with immunological or endometrial
pathologies were not included. For identication of CD68+ macrophages,
CD117+ em cells and NOTCH1+ em cells, all samples were
immunohiochemically ained with the respective antibodies. Evaluation
of the positively ained romal cells was performed by microscopic
observation of multiple tissue areas. Results were presented as percentage
of positively ained romal cells. Statiics: SPSS v.21.
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In the mid-secretory endometrial roma of the udied patients 0.55%
(0.07-14.44%) CD68+ macrophages, 0.02% (0-0.21%) CD117+ em
cells and 0.062% (0-2.1%) NOTCH1+ em cells were found. Spearman
correlation analysis revealed low, but signicant positive relation between
CD68+ macrophages and CD117+ em cells percentages (R=0.216,
p=0.025), while no correlation was observed with NOTCH1+ em cells
percentage (R=0.150, p=0.123).
In conclusion, the observed correlation between CD68+ macrophages
and CD117+ em cells, and lack of relation to NOTCH+ em cells, sugges
a possible regulation of the macrophages endometrial diribution by the
local CD117+ em cells or vice versa. These ndings demonrate that there
is a CD117+ em cell to immune cell communication in the endometrial
roma that could be associated to fertility and should be further udied.
Acknowledgment: This work was supported by Soa University Science Fund
under the grand N 80-10-65/10.05.2022
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