Tracing the Glycogen Cells with Protocadherin 12 During Mouse Placenta Development

Abstract

Among the different trophoblast subtypes of the mouse placenta, the glycogen cells (GC) are one of the trophoblast subtypes that invade the decidua. We previously established that GC specifically expressed protocadherin 12 (PCDH12). In this paper, we investigated the origin of the PCDH12-positive cells and we characterized their fate in the maternal tissues. Our data indicate that they directly originate from the central part of the ectoplacental cone at embryonic day (E) 7.5. PCDH12-positive cells start to accumulate glycogen from E10.5 and the first migrating cells could be observed from this age. Unlike other placental and decidual cells, GC do not express P-cadherin, which may explain their migration properties in this organ. In the decidua, GC settle in the vicinity of the maternal vascular sinuses but do not incorporate in the endothelium. By the end of gestation (E17.5), most GC islets of the decidua enter into a lytic phase and form large lacunae. These lacunae, filled with glycogen, may provide a substantial source of energy at the end of gestation or during delivery. Our data suggest that spongiotrophoblasts and GC are two independent lineages and we bring insights into GC migration and fate.Bouillot et al.

Origin and characteristics of glycogen cells in the developing murine placenta

“…We predict that these cells correspond to early pre-GCs that have not accumulated sufficient glycogen stores to exhibit the classic vacuolated appearance of GCs following fixation and embedding. Furthermore, these cells are distinct from spongiotrophoblasts, representing a discreet trophoblast lineage that may express protocadherin12 (Bouillot et al, 2006). Ultrastructural study on placental sections show pre-GCs, surrounded by extracellular matrix and beginning to accumulate glycogen granules ( Fig.…”

“…However, Bouillot et al recently described expression of protocadherin12 in a discrete population of ectoplacental cone cells, which were later in gestation identified as GCs (Bouillot et al, 2006).…”

“…A group of cells in the central part of the EPC were found to express protocadherin12 (PCDH12). This PCDH12 marker was later shown to be expressed exclusively by the GCs (Rampon et al, 2005;Bouillot et al, 2006). Apart from their transitory behavior and accumulation of glycogen, not much more is known about the function of GCs.…”

Sp1/Sp3 compound heterozygous mice are not viable: Impaired erythropoiesis and severe placental defects

“…We performed in situ hybridization with a probe for prolactin-like protein C3 (Prlpc3), specifically expressed in spongiotrophoblast cells (D. Simmons, unpublished observations), and protocadherin 12 (Pcdh12), specifically expressed in glycogen cells (Bouillot et al, 2006) of the spongiotrophoblast cell layer and the decidua. Prlpc3 staining was significantly reduced, and only very few Pcdh12-positive glycogen cells were detected in Sp1/Sp3 compound heterozygous and Sp3 Figure S3), indicating a reduction in both spongiotrophoblast and trophoblast glycogen cells in Sp1/Sp3 compound heterozygous and Sp3 null placentae.…”

Protocadherin-12 Cleavage Is a Regulated Process Mediated by ADAM10 Protein

“…Unlike classical cadherins, Pcdh12 ectopic expression was unable to inhibit cell migration from a confluent monolayer of transfected cells (20). In the mouse, Pcdh12 is highly expressed in several cell types: (i) in a specific type of trophoblast called the "glycogen cells" that emerge in the placenta and invade the maternal decidua; (ii) in the mesangial cells of kidney glomeruli; and (iii) in angiogenic endothelial cells, whereas its expression is reduced in resting endothelium (21,22). Pcdh12-deficient mice were alive and fertile but showed alterations in placental development that resulted in embryonic growth retardation (23).…”