Placental iron deposition and altered FOXP3/PGF expression in pregnancies complicated by HbH disease.

OBJECTIVE: This study aimed to characterize the clinical and placental features of pregnancies complicated by haemoglobin H (HbH) disease and to explore potential associations among iron-related changes, FOXP3 expression, and placental growth factor (PGF) expression. METHODS: Clinical comparisons, placental histological examinations, in vitro trophoblast models, transcriptomic and bioinformatic analyses, and molecular assays were performed to investigate placental iron-related changes and the relationship between FOXP3 and PGF expression in HbH disease. RESULTS: Women with HbH disease were more likely to have pregnancies with at least one recorded complication and persistently elevated serum ferritin levels, together with an abnormal placental villous morphology and iron deposition in syncytiotrophoblasts. Holo-transferrin treatment was associated with increased PGF expression in trophoblast models. FOXP3 expression and its enrichment at the PGF promoter were also altered upon transferrin treatment, suggesting a potential relationship between FOXP3 and PGF regulation. Increased PGF immunoreactivity was also detected in placental tissues from women with HbH disease. CONCLUSIONS: HbH disease during pregnancy is associated with placental iron deposition and altered FOXP3/PGF expression. These findings suggest a possible link between iron-related conditions and FOXP3/PGF regulation in trophoblasts; however, the causal relationships among these alterations and their contributions to adverse pregnancy outcomes require further investigation.