Proteoglycans: Systems-Level Insight into Their Expression in Healthy and Diseased Placentas

Abstract

Proteoglycan macromolecules play key roles in several physiological processes (e.g., adhesion, proliferation, migration, invasion, angiogenesis, and apoptosis), all of which are important for placentation and healthy pregnancy. However, their precise role in human reproduction has not been clarified. To fill this gap, herein, we provide an overview of proteoglycans’ expression and role in the placenta, in trophoblast development, and in pregnancy complications (pre-eclampsia, fetal growth restriction), highlighting one of the most important members of this family, syndecan-1 (SDC1). Microarray data analysis showed that of 34 placentally expressed proteoglycans, SDC1 production is markedly the highest in the placenta and that SDC1 is the most upregulated gene during trophoblast differentiation into the syncytiotrophoblast. Furthermore, placental transcriptomic data identified dysregulated proteoglycan genes in pre-eclampsia and in fetal growth restriction, including SDC1, which is supported by the lower concentration of syndecan-1 in maternal blood in these syndromes. Overall, our clinical and in vitro studies, data analyses, and literature search pointed out that proteoglycans, as important components of the placenta, may regulate various stages of placental development and participate in the maintenance of a healthy pregnancy. Moreover, syndecan-1 may serve as a useful marker of syncytialization and a prognostic marker of adverse pregnancy outcomes. Further studies are warranted to explore the role of proteoglycans in healthy and complicated pregnancies, which may help in diagnostic or therapeutic developments.

Identification of the Mechanism of Action of the Index Components of Banxia Xiexin Decoction for Gastric Cancer through Network Pharmacology, Bioinformatics, and Molecular Docking Analysis

“…Proteoglycans are essential in cancer progression directly and through their interactions with other molecules, including growth factors and cytokines. Some proteoglycans function as tumor suppressors [36]. Recent evidence from a cohort study suggested that overexpression of extracellular proteoglycan biglycan may serve as a possible prognostic biomarker and therapeutic option for patients with advanced gastric cancer [37].…”

Transcriptome profiling analysis of uterus during chicken laying periods

“…SDC1 play an important role in the placenta, in trophoblast development, and in pregnancy complications, highlighting one of the most important members of this family. Proteoglycan macromolecules play key roles in several physiological processes (e.g., adhesion, proliferation, migration, invasion, angiogenesis, and apoptosis), all of which are important for placentation and healthy pregnancy [80]. BTC was shown to be expressed exclusively at the sites of blastocyst apposition in the mouse uterus, suggesting an involvement in embryo implantation [81].…”

Revealing the molecular landscape of human placenta: a systematic review and meta-analysis of single-cell RNA sequencing studies

“…Using ISH and immunohistochemistry, LAIR2 was shown to be expressed only in the more distal portions of CCC and the invading EVT in the first trimester placentas, while no expression was observed in any other fetal cells ( Founds et al , 2010 ). From the microarray profiling of CTB and EVT extracted from the first trimester placentas, ACAN was shown to be overexpressed in EVT compared to CTB ( Oravecz et al , 2022 ). In contrast, HTRA4 expression was shown to increase during syncytialization of BeWo cells ( Mansilla et al , 2021 ) and in term placentas, HTRA4 protein localizes mainly to STB using immunohistochemistry ( Liu et al , 2018a ).…”