ArticleLaboratory investigation; a journal of technical methods and pathology2017
GDM alters paracrine regulation of feto-placental angiogenesis via the trophoblast.
Article in Laboratory investigation; a journal of technical methods and pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
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- First-trimester biomarkers of gestational diabetes mellitus: A scoping review.Acta obstetricia et gynecologica Scandinavica · 2025Article
- Kisspeptin and neurokinin B: roles in reproductive health.Physiological reviews · 2025Review
- Study and validation on mitochondrial and immune-related hub genes in gestational diabetes mellitus based on bioinformatics.Frontiers in endocrinology · 2025Article
- Influence of gestational diabetes mellitus on the cardiovascular system and its underlying mechanisms.Frontiers in endocrinology · 2025Review
- Placental structural adaptation to maternal physical activity and sedentary behavior: findings of the DALI lifestyle study.Human reproduction (Oxford, England) · 2024Article
- High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress.Open life sciences · 2023Article
- CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta.Frontiers in cell and developmental biology · 2023Article
- Fetoplacental oxygen homeostasis in pregnancies with maternal diabetes mellitus and obesity.Nature reviews. Endocrinology · 2022Review
- The Role of Kisspeptin in the Pathogenesis of Pregnancy Complications: A Narrative Review.International journal of molecular sciences · 2022Review
- Kisspeptin in the Prediction of Pregnancy Complications.Frontiers in endocrinology · 2022Review
- Effects of Early Nursing Monitoring on Pregnancy Outcomes of Pregnant Women with Gestational Diabetes Mellitus under Internet of Things.Computational and mathematical methods in medicine · 2022Article
- Construction of a novel miRNA regulatory network and identification of target genes in gestational diabetes mellitus by integrated analysis.Frontiers in genetics · 2022Article
- Placental structural abnormalities in gestational diabetes and when they develop: A scoping review.Placenta · 2021Article
- Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta.International journal of molecular sciences · 2021Review
- Placental secretome characterization identifies candidates for pregnancy complications.Communications biology · 2021Article
- Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVEC angiogenesis in vitro.Stem cell research & therapy · 2021Article
- Altered Expression of Angiogenic Biomarkers in Pregnancy Associated with Gestational Diabetes.International journal of general medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Feto-placental angiogenesis and vascular development are tightly regulated by pro- and anti-angiogenic factors. Villous trophoblast may be a major source of these factors. It forms the classical placental barrier between mother and fetus, and is thus exposed to maternal influences as well. Metabolic and hormonal derangements in gestational diabetes mellitus (GDM) affect feto-placental angiogenesis and vascular growth. Here we hypothesized that GDM alters the trophoblast secretome, which will modulate the paracrine regulation of feto-placental angiogenesis. Primary term trophoblasts were isolated from normal (n=6) and GDM (n=6) pregnancies. Trophoblast conditioned medium (CM) was used to investigate paracrine effects of normal and GDM-exposed trophoblasts on feto-placental endothelial cells (fpECs; n=7), using functional assays for 2D network formation, wound healing, chemotaxis, and proliferation. Gene expression of 23 pro- and anti-angiogenic factors was analyzed. Four trophoblast-derived paracrine regulators of angiogenesis were specifically measured in CM. CM from GDM trophoblasts increased 2D network formation of fpEC by 2.4-fold (P<0.001), whereas wound healing was attenuated by 1.8-fold (P=0.02) and chemo-attraction to the CM was reduced by 33±9% (P=0.02). The effect of CM on proliferation was unchanged between normal and GDM trophoblasts. Expression analysis of pro- and anti-angiogenic molecules in normal and GDM trophoblasts revealed significant differences in ANGPT2, HGF, KISS1 and PLGF expression. Analysis of secreted proteins demonstrated reduced pigment epithelium derived factor and tumor necrosis factor-α secretion by GDM trophoblasts. GDM alters the balance of trophoblast derived, angiogenesis modulating paracrine factors. This may contribute to GDM-associated changes in placental angiogenesis and vascular structure.
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