In vitro exposure to the SARS-CoV-2 Spike protein subunit S1 leads to changes in several functional characteristics of human trophoblast cells
Year: 2026
Type: article
Abstract: : Introduction By directly regulating nutrient supply and fetal growth, the placenta plays a central role in fetal programming. The extent to which SARS-CoV-2 maternal infection during pregnancy will affect the long-term metabolic health of the newborn is yet to be explored. As trophoblast cells express the ACE2 (angiotensin converting enzyme 2) receptor, we aimed to investigate the potential fetal programming effects of SARS-CoV-2 Spike protein S1 subunit (Spike S1), by focusing on nutrient transport. Methods We investigated the in vitro effect of Spike S1 (100 ng/mL; 24h) on two in vitro models of human trophoblasts, primary cultured human trophoblasts and the BeWo cell line. Results Spike S1 elicited an inflammatory response, caused a low grade cytotoxic and antiproliferative effect and, in the more actively replicating BeWo cell line, induced G2-M cell cycle arrest. Moreover, it interfered with the activities of the glucose transporter GLUT1 (facilitative glucose transporter 1) and the folic acid transporter RFC1 (reduced folate carrier 1), and altered the gene expression of the aminoacid transporters LAT1 (L-type amino acid transporter 1) and y + LAT2 (y + L-type amino acid transporter 2). It also markedly increased mTOR (mammalian target of rapamycin) gene expression in primary cultured trophoblasts. Discussion We conclude that the Spike S1 subunit induces some changes in trophoblast metabolic parameters that may be of relevance for fetal programming metabolic disease in the adult.
Source: Placenta
Authors: Francisca Carmo, Ilda Rodrigues, Carla Ramalho, Fátima Martel
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,720
Award: G3093644527
OpenAlex ID: W7125410900