Abstract
BackgroundIn normal mammalian development a high percentage of implantations is lost by spontaneous resorption. This is a major problem in assisted reproduction and blastocyst transfer. Which embryo will be resorbed is unpredictable. Resorption is very fast, so that with conventional methods only final haemorrhagic stages are encountered.Here we describe the histology and immunohistochemistry of 23 spontaneous embryo resorptions between days 7 and 13 of murine development, which were identified by high-resolution ultrasound (US) in a previous study.ResultsIn the early resorptions detected at day 7, the embryo proper was replaced by maternal haemorrhage and a suppurate focus of maternal neutrophils. In the decidua maternal macrophages transformed to foam cells and formed a second focus of tissue dissolution.In the late resorptions detected at day 9, the embryo underwent apoptosis without involvement of maternal cells. The apoptotic embryonic cells expressed caspase 3 and embryonic blood cells developed a macrophage like phenotype. Subsequently, the wall of the embryonic vesicle ruptured and the apoptotic embryo was aborted into the uterine lumen. Abortion was initiated by degeneration of the embryonic lacunar trophoblast and dissolution of the maternal decidua capsularis via sterile inflammation and accompanied by maternal haemorrhage, invasion of the apoptotic embryo by maternal neutrophils, and contraction rings of the uterine muscle layers.ConclusionsWe conclude that spontaneous resorption starts with endogenous apoptosis of the embryo without maternal contribution. After break down of the foetal-maternal border, the apoptotic embryo is invaded by maternal neutrophils, aborted into the uterine lumen, and rapidly resorbed. We assume that the innate maternal unspecific inflammation is elicited by disintegrating apoptotic embryonic cells.Graphical abstract
Highlights
In normal mammalian development a high percentage of implantations is lost by spontaneous resorption
The goal of the present study is to identify the mechanism of spontaneous resorption in normal pregnancies
Study outline In the current study, we describe the histology and immunohistochemistry of spontaneous resorptions, which were identified by reduced growth rate and reduced heart rate in daily scans of pregnant mice with highresolution ultrasound in a previous study [15]
Summary
In normal mammalian development a high percentage of implantations is lost by spontaneous resorption. This is a major problem in assisted reproduction and blastocyst transfer. In normal development of mammals, a high percentage of blastocysts are lost before or after implantation by spontaneous resorption. Early embryonic loss rate in cattle amounts to over 30% [4] and is estimated to reach 14% post implantation [5]. In vivo ultrasonographic studies in the dog and horse present a post implantation resorption rate of over 10% [6] and 8% [7] respectively. These findings correspond to the resorption rate of 10% observed in our study
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