Pregnancy-Specific Glycoproteins and Maternal-Fetal Interactions

Pregnancy-specific glycoproteins (PSGs) are a family of immunoglobulin superfamily members secreted by placental syncytiotrophoblast cells, reaching high concentrations in maternal circulation during gestation. They orchestrate key maternal–fetal interactions by modulating immune tolerance, promoting angiogenesis and supporting trophoblast invasion into the uterine decidua. PSGs bind to cell surface receptors such as integrins and glycosaminoglycans to trigger intracellular signalling cascades, including calcium-dependent and SMAD pathways, that underpin endothelial tubulogenesis and immune cell differentiation. Dysregulation of PSG expression or function has been implicated in pregnancy complications, notably preeclampsia, characterised by insufficient trophoblast invasiveness and impaired vascular adaptation. Beyond human pregnancy, comparative studies in rodents, equids and other mammals reveal convergent evolution of PSG-like molecules that facilitate invasive placentation. Advances in organoid modelling and genome editing now enable functional dissection of PSGs in vitro, offering new avenues for biomarker discovery and therapeutic targeting to safeguard maternal and fetal health worldwide.

Research from Nature Portfolio

Recent studies have uncovered how endogenous retroviral elements act as regulatory enhancers for trophoblast genes, including members of the PSG family. Using epigenomic profiling of primary human trophoblast cells, researchers identified primate-specific retroviral long terminal repeats located near key placental genes that are bound by placental transcription factors. Functional editing of several of these elements demonstrated enhancer activity on genes such as PSG5, as well as on endoglin (ENG), a co-receptor implicated in preeclampsia through modulation of soluble endoglin secretion. This work highlights the contribution of transposable elements to the dynamic regulation of PSG expression and suggests that variation in these regulatory sequences may influence pregnancy outcome.

Pregnancy-Specific Glycoproteins and Maternal-Fetal Interactions publication trend

The graph below shows the total number of articles in pregnancy-specific glycoproteins and maternal-fetal interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Pregnancy-Specific Glycoprotein (PSG): A family of secreted placental proteins that modulate maternal immune and vascular responses.

Trophoblast: The outer cell layer of the embryo that invades the uterine lining and forms the placenta.

Store-Operated Calcium Entry (SOCE): A cellular process by which depletion of endoplasmic reticulum calcium stores triggers calcium influx through Orai channels.

Integrin α5β1: A cell surface receptor that binds extracellular matrix components and mediates cell adhesion and migration.

Preeclampsia: A pregnancy disorder marked by hypertension and organ dysfunction, often associated with impaired placental development.

References

1. Regulation of human trophoblast gene expression by endogenous retroviruses. Nature Structural & Molecular Biology (2023).
2. Production of Mare Chorionic Girdle Organoids That Secrete Equine Chorionic Gonadotropin. International Journal of Molecular Sciences (2023).
3. Pregnancy-Specific Beta-1-Glycoprotein 1 Increases HTR-8/SVneo Cell Migration through the Orai1/Akt Signaling Pathway. Biomolecules (2024).
4. Pregnancy-Specific Glycoprotein 9 Enhances Store-Operated Calcium Entry and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells. Diagnostics (2023).
5. Evolution of Placental Hormones: Implications for Animal Models. Frontiers in Endocrinology (2022).
6. Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin α5β1 Is a Modulator of Extravillous Trophoblast Functions. Cells (2019).
7. Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans*. Journal of Biological Chemistry (2010).