Comparative Label-Free Proteomics of a High-Glucose Syncytialised Trophoblast Model Identifies Mitochondrial Fission Factor (MFF) as a Candidate Serum Biomarker Associated with Hyperglycaemic Pregnancy
Year: 2026
Type: article
Abstract: Placental protein markers of maternal hyperglycaemia in gestational diabetes mellitus (GDM) remain scarce. We aimed to find trophoblast proteins that change under high glucose and to test whether a lead candidate is also raised in maternal serum. In our established insulin-resistant model, we used label-free liquid chromatography–tandem mass spectrometry (LC-MS/MS) to compare BeWo cells syncytialised with forskolin/8-Br-cAMP in high-glucose (25 mM) medium, with or without vascular endothelial growth factor (VEGF), with undifferentiated control cells in normoglycaemic (5 mM) medium (n = 3 per group); glucose and differentiation therefore varied together. Of 3528 protein groups, 388 were differentially abundant (24 at Benjamini–Hochberg q < 0.05). Mitochondrial fission factor (MFF), the outer-membrane receptor for dynamin-related protein 1 (DRP1), increased 4.5-fold (q = 0.040), whereas DRP1 was unchanged; mitochondrial calcium-uniporter components, pyruvate dehydrogenase kinase 3 and glycogen synthase 1 also increased. VEGF did not alter this signature (MFF: 0.91-fold, p = 0.71). Enzyme-linked immunosorbent assay (ELISA) confirmed higher MFF in high-glucose cell lysates (+48%) and, independently of in vitro differentiation, in gestational-day-7 serum of streptozotocin-treated hyperglycaemic pregnant rats (+41%; both p < 0.001; n = 3 per group), consistent with reported increases of MFF in GDM placentae. As serum was sampled after hyperglycaemia developed, these data show association, not prediction. MFF is a candidate serum biomarker of hyperglycaemic pregnancy; studies separating glucose from differentiation and validation in women are needed.
Source: Cells
Institution: Lovely Professional University
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,258
OpenAlex ID: W7225609844