Expression of the Pregnancy-Specific β1-Glycoprotein Gene in Cultured Human Trophoblasts

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Abstract
Human pregnancy-specific .beta.1-glycoprotein (PS.beta.G), the major placental glycoprotein, shares strong sequence similarity with carcinoembryonic antigen and is a member of the immunoglobulin superfamily. To understand the role of PSG.beta.G in placental ontogeny during pregnancy, we examined its synthesis and regulation in primary cultures of trophoblast cells. Freshly plated (12 h) cytotrophoblasts expressed little PS.beta.G transcripts; however, within 24 h of culture, PS.beta.G mRNAs became detectable. PS.beta.G synthesis and mRNA expression increased with time in culture, and maximal synthesis was achieved at 4 days, indicating that primary trophoblasts continue differentiating in vitro. Molecular cloning revealed that PS.beta.G is an extremely polymorphic protein. Most PS.beta.G cDNAs identified to date, including the three cDNAs (PSG16, PSG93, and PSG95) isolated in this laboratory, share strong sequence similarity in the 5'' (designated PSG-5'') and coding regions, but differ in sequences at the 3'' region. The PSG-5'', PSG93-specific, PSG16/PSG93-3'' and PSG95-3'' probes, which identify the majority of PS.beta.G mRNAs, hybridized with three mRNAs of 2.3, 2.2, and 1.7 kilobases in primary trophoblasts and human term placental tissue. Ribonuclease protection analysis demonstrated that primary trophoblasts expressed most of the placental placental PS.beta.G transcripts. However, culturing in vitro altered PS.beta.G gene expression, and the level of PS.beta.G transcripts containing a PSG95-3'' sequence was preferentially increased in primary trophoblasts. Moreover, primary trophoblasts synthesized a 64K PS.beta.G polypeptide in variable amounts and three PS.beta.Gs of 72K, 62K, and 54K in roughly equal amounts, whereas purified human term placental PS.beta.G consists of a major polypeptide of 72K and two minor ones of 64K and 54K. PS.beta.G gene expression in primary trophoblasts was slightly reduced by 8-bromo-cAMP but was markedly inhibited by sodium butyrate.
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