Coordinate Expression of Splice Variants of the Murine Pregnancy‐Specific Glycoprotein (PSG) Gene Family During Placental Development

Abstract

The human and murine pregnancy-specific glycoprotein (PSG) gene families encode a large number of closely related proteins which are abundantly expressed in the fetal trophoblast and secreted into the maternal circulation. Although the presence of a well conserved tripeptide sequence His or Arg-Gly-Asp or Glu or Lys (H/RGD/E/K) similar to the RGD motif found in extracellular matrix proteins hints towards a possible interaction with integrin-type receptors, the function of this group of proteins related to the carcinoembryonic antigen family is still unknown. It is also not clear whether the various members of the PSG family exert the same function. Here we describe the cloning of two splice variants of Cea4 (Ceda, Cea4b), a murine PSG family member, which lacks the RGD-related consensus motif. Cea4a, like most of the other rodent PSG members, is composed of three immunoglobulin (Ig) variable-like domains (Nl-N3) and and one Ig constant-like domain (A). In contrast, Cea4b lacks the N2 domain (NIN3A), demonstrating for the first time that PSG isoforms produced by alternative splicing also exist in mice. The mRNAs coding for Cea4a and Cea4b exhibit the same expression kinetics during placental development as found for two other murine PSGs, Cea2 and Cea3, which contain the RGD-like motif. Expression starts after day 12.5 of embryonic development (El 2.5) and maximum steady-state levels are reached around E15.5 -E17.5 as determined by RNase protection analyses. At E17.5, PSG transcripts can be detected exclusively in the spongiotrophoblast of the placenta. In addition, PCR analyses revealed that Cea2, Cea3, and Cea4 transcripts are also found in RNA from a pool of embryos (E12-El5) but are absent from a number of adult tissues tested (kidney, lung, testis, ovary, liver, brain, thymus, heart, spleen). These results indicate that the various PSG isoforms exert their function(s) at the same time during placental and embryonic development.

Imprinted genes in mouse placental development and the regulation of fetal energy stores

“…These glycogen stores are thought to provide a source of energy for late-gestation embryonic growth and parturition (Coan et al 2006). In contrast, the spongiotrophoblast cells, which form the bulk of the junctional zone, are thought to perform an endocrine role in synthesising and secreting a range of prolactin-related (Prl) proteins and pregnancy-specific glycoproteins (Psgs) that act to modulate maternal physiology in response to pregnancy (Kromer et al 1996, Wynne et al 2006, Simmons et al 2008b). …”

Psg18 Is Specifically Expressed in Follicle-associated Epithelium

“…1). This observation is intriguing, considering that Psg family members are believed to be expressed exclusively in the placenta (Kromer et al, 1996).…”

“…Psgs are the most abundant fetal proteins in the maternal bloodstream at the late stage of pregnancy (Lin et al, 1974). Their almost exclusive synthesis by trophoblasts of the haemochorial placenta in rodents and primates is well documented (Kromer et al, 1996;Lei et al, 1992). Multiple lines of evidence suggest that Psg modulates the maternal immune system to prevent rejection of the allotypic fetus.…”

Tpbpa mediated deletion of Tfap2c leads to deregulation of MAPK, P21, AKT and subsequent placental growth arrest

“…These are synthesized by the TGCs and SpT cells in the mouse placenta and syncytiotrophoblast cells in the human placenta (Kromer et al, 1996;Wynne et al, 2006;Zhou et al, 1997). In humans, reduced levels of placental lactogens and pregnancy-specific glycoproteins in the maternal blood are associated with impaired placental function, leading to conditions such as IUGR and preeclampsia (Bersinger and Odegard, 2004;Pihl et al, 2009).…”

“…4B). The pregnancy-specific glycoprotein (Psg) and carcinoembryonic antigen-related adhesion molecules (CEACAMs) are synthesized by the TGCs and SpT cells in the mouse placenta (Kromer et al, 1996;Wynne et al, 2006;Zhou et al, 1997). Interestingly, many of the downregulated genes in the mutant placentae belong to the CEA family (Psg18, Psg22, Psg23, Ceacam13, Ceacam14, Ceacam3) and prolactin-associated protein family (Prl4a1, Prl3c1, Prl7c1, Prlpc3) (Fig.…”