Fig. 1. Maternal iron overload and systemic inflammation synergize to cause embryotoxicity.

Dietary iron loading was achieved by feeding WT mice a high iron diet (light blue circles, 2500–5000 ppm iron) for 1–3 weeks before mating and during pregnancy. Hepcidin KO dams (dark blue circles), a model of genetic iron loading, were fed standard diet (185 ppm iron). Both dietary and genetic iron loaded pregnancies were compared to iron-adequate pregnancies (WT females fed standard diet, gray circles) under normal conditions and with maternal inflammation. a Maternal systemic inflammation was induced on E8.5 by a single subcutaneous injection of 0.5 μg/g LPS in the interscapular area and dams were euthanized on E18.5: b embryo gross morphology, c incidence of adverse pregnancy outcome, d embryo loss and e embryo malformation. f Incidence of embryo malformation by type. g Maternal systemic inflammation was induced on E15.5 by a single subcutaneous injection of 0.5 μg/g LPS for 24 h: h embryo gross morphology, i incidence of preterm birth and j embryo resorption. k Incidence of embryo outcome by type. c–e, i, j Error bars represent mean ± s.e.m. Statistical differences were determined by two-way ANOVA followed by Holm-Sidak method for multiple comparisons. ^&P < 0.05, ^&&P < 0.01, ^&&&P < 0.001, ^&&&&P < 0.0001. Source data are provided as a Source data file.