Morphofunctional features of the uteroplacental unit and mouse embryo in the early stages of experimental miscarriage
Authors: Artemyeva K.A. , Bogdanova I.M. , Stepanova I.I. , Boltovskaya M.N. , Stepanov A.A. , Ponomarenko E.A. , Kalyuzhin O.V. , Zemlyakov A.E. , Dambaeva S.V. 
Published: October 2020

Introduction. The majority of cases of habitual miscarriage are closely related to impaired maternal immune tolerance. Experimental mice models of abortion, where the critical time points are established to monitor pregnancy progression, are widely used to study the pathogenesis of early reproductive loss. However, the relationship between the embryonic development and extraembryonic structures with the immune microen-vironment is not well understood. The aim of the study is to compare the morphofunctional characteristics of the uteroplacental unit and embryo in early pregnancy in mice with experimental spontaneous, induced, and potentiated abortions. Materials and methods. Allogeneic physiological pregnancy was modeled using ♀CBA × ♂BALB/c mice mating. Spontaneous abortions were reproduced by mating ♀CBA × ♂DBA/2 mice. Induced abortions and potentiated abortions were triggered by intraperitoneal administration of the immunomodulator ß-heptylglycoside muramyl dipeptide (MDP) to pregnant females on gestation day (gd) 5 and gd 7 mated in following combinations ♀CBA × ♂BALB/c and ♀CBA × ♂DBA/2, respectively. Mice were withdrawn from the experiment on gd 8, then uterine horns and uteroplacental units were isolated. The material was fixed in 10% neutral formalin, and standard processing was performed for histological examination. In equatorial sections, the cross-sectional area of uteroplacental unit was measured, and maternal, embryonic, as well as extraembryonic structures were analyzed. An immunohistochemical assay with rabbit polyclonal anti-CD68 antibodies was conducted to detect macrophages, then the density of CD68+ cells per 1 mm2 of the decidual area was determined. Results. On day 8 of pregnancy, in the groups of induced and potentiated abortions cross-sectional area of the uteroplacental units was decreased compared with the groups of physiological pregnancy and sponta-neous abortions. Induced and potentiated abortions demonstrated vasodilation in the mesometric decidua zone and stagnation of blood in the blood vessels, compaction of trophoblast, and hemorrhage in decidua basalis whether spontaneous abortions showed occluded maternal vessels surrounded by edematous and vacuolated trophoblast cells.At the early stages of modeling of spontaneous and immuno-dependent abortions, disturbances in the devel-opment of the embryo and extraembryonic structures were revealed, ranging from initial signs of resorption to the destruction of the embryo and membranes.In viable embryos, density indices of CD68+ macrophages in the decidual membrane of the uteroplacental units did not differ significantly in all miscarriage cases, CD68+ cells were not detected in cases of embryo-nal resorption. Conclusion. The MDP treatment in a period after completion of implantation and before forming a mature placenta (gd 5–7) results in the inducing or the potentiating abortions in CBA females mated with by Balb/c or DBA/2 males, respectively. In both cases, we revealed disturbed chorion morphogenesis and embryonic development to the extent of its complete resorption and the absence of CD68+ macrophages in resorbed embryos’ microenvironment on day 8 of pregnancy. Keywords: miscarriage, models, muramyl dipeptide β-heptylglycoside, uteroplacental unit, macrophages, immunotolerance