Abstract
The placenta mediates the exchange of factors such as gases and nutrients between mother and fetus and has specific demands for supply of blood from the maternal circulation. The maternal uterine vasculature needs to adapt to this temporary demand and the success of this arterial remodeling process has implications for fetal growth. Cells of the maternal immune system, especially natural killer (NK) cells, play a critical role in this process. Here we describe a method to assess the degree of remodeling of maternal spiral arteries during mouse pregnancy. Hematoxylin and eosin-stained tissue sections are scanned and the size of the vessels analysed. As a complementary validation method, we also present a qualitative assessment for the success of the remodeling process by immunohistochemical detection of smooth muscle actin (SMA), which normally disappears from within the arterial vascular media at mid-gestation. Together, these methods enable determination of an important parameter of the pregnancy phenotype. These results can be combined with other endpoints of mouse pregnancy to provide insight into the mechanisms underlying pregnancy-related complications.
Highlights
The exchange of nutrients, gases and waste products during eutherian gestation is mediated by the placenta
While the underlying mechanisms differ in detail between human and murine pregnancy, the final result of the remodeling process in both species is dilated, high conductance vasculature that loses its smooth muscle layer
The interstitial and endovascular invasion of extravillous trophoblast and their interaction with uterine natural killer (uNK) cells are important for inducing vascular changes and promoting fetal growth8-10. uNK cells can orchestrate human trophoblast invasion through chemokines[11] and cytokines such as granulocyte macrophage - colony stimulating factor (GM-CSF)[12]
Summary
The exchange of nutrients, gases and waste products during eutherian gestation is mediated by the placenta. Mice that lack either NK cells or components of the IFN-γ signaling pathway fail to undergo these changes and this is associated with reduced fetal growth[6,7], stressing the importance of an adequate blood supply to the fetoplacental unit. The interstitial and endovascular invasion of extravillous trophoblast and their interaction with uNK cells are important for inducing vascular changes and promoting fetal growth. Shallow trophoblast invasion is associated with reduced arterial remodeling and pregnancy complications such as pre-eclampsia[9]. This protocol is based on the pioneering work of Anne Croy who described the important role of the immune system and NK-derived IFN-γ for successful vascular remodeling through immunohistochemistry and elegant transfer experiments[5,13].
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