Functional Consequences of Cell Type-Restricted Expression of Laminin α5 in Mouse Placental Labyrinth and Kidney Glomerular Capillaries

The labyrinth is the highly vascularized part of the rodent placenta that allows efficient transfer of gases, nutrients, wastes, and other molecules between the maternal and embryonic circulations. These two blood compartments are separated by blastocyst-derived trophoblasts and endothelial cells with an intervening basement membrane that contains laminin and other typical basement membrane components. Previously we reported that the labyrinth of laminin alpha 5 knockout (LM alpha 5-/-) embryos exhibits reduced vascularization and detachment of endothelial cells from the basement membrane, which normally contains LM alpha 5. As very little is known about the origin of this vascular basement membrane, we investigated the cellular requirements for LM alpha 5 expression in the mouse placental labyrinth. By fluorescence-activated cell sorting and RTPCR we confirmed that both endothelial cells and trophoblasts normally express LM alpha 5. Using Cre-loxP technology and doxycycline-mediated gene expression, we generated genetically mosaic placentas in which either the trophoblasts or the endothelial cells, but not both, expressed LM alpha 5. We found that the overall architecture of the labyrinth was normal as long as one of these two cell types expressed LM alpha 5, even if it was transgene-derived human laminin alpha 5. These results suggest that laminin trimers containing alpha 5 that are synthesized and secreted by endothelium or by trophoblasts are capable of integrating into the basement membrane and promoting normal vascularization of the placenta. Additional studies showed that endothelium-expressed human LM alpha 5 can support vascularization of the kidney glomerulus, consistent with previous studies using a tissue grafting approach.