Galectin-3 deficiency in pregnancy increases the risk of fetal growth restriction (FGR) via placental insufficiency

摘要

a Macroscopic appearance of the implantation sites on embryonic day (E)13. The pictures show the normal phenotype of Lgals3+/+ (WT) compared to Lgals3−/− (KO) dams, which exhibit resorbed fetuses (left panel, bar = 1 cm). Abortion rate (%) was calculated on E13 as follows: abortion rate = (fetal resorptions x 100)/total number of implantations (right panel, n = 19–24). b Fetal body weight (in grams) of E13 and E17 fetuses carried by Lgals3+/+ (WT) or Lgals3−/− (KO) dams (left panel, n = 13–21). Theiler stage developmental analysis on E13, upper arrows show that pinna is not turned forward and lower arrows show absence of separated fingers in KO fetuses (bar = 0.25 cm). On E17, upper arrows display fewer skin wrinkles, smaller whiskers, and lower arrows show that eyes are clearly visible through the eyelids in gal-3 KO fetuses (bar = 0.5 cm) (right panel). c Mean body weights of pups from Lgals3+/+ and Lgals3−/− dams. Reduced neonatal body weight was observed in Lgals3 KO offspring, which persisted until postnatal day (P)14 (n = 55–161). d E17 asymmetrical FGR as identified by fetal brain-to-liver weight ratio (n = 15–30). e Placental weight (mg) observed on E13 and E17 (left panel, n = 13–21). H&E histological analysis of E10 and E13 implantation sites shows an enlarged decidua in Lgals3−/− mice (middle panel, bar = 500 μm). Isolectin B4 (IB4) analysis of placental depth related to the decidua was significantly lower in placentas of Lgals3 KO mice (right panel, n = 7–8). f Accumulation of mature NK cells (PAS+DBA+) were significantly elevated at E13 (left panel, bar = 500 μm, n = 15) and their perforin granules (arrows) were released in gal-3 deficient pregnancy (right panel, bar = 50 μm, n = 8–11). g Progesterone levels measured in E13 serum by ELISA (n = 5). h Quantitative PCR (qPCR) analysis of decidual IFN-Ƴ, TNF-α, TGF-β, IL-10, and IL-17 gene expression in Lgals3+/+ (WT) and Lgals3−/− (KO) dams at E7 (n = 4–9). In all figures, data are expressed as mean ± SEM. *P < 0.05, †P < 0.01, and ‡P < 0.001 using two-tailed t test.