Figure 1
Figure 1. EVs impair embryonic and placental development and cause a PE-like phenotype in mice. (A-D) Impaired pregnancy outcome in C57BL/6 mice at day 12.5 p.c. following IV injection of mouse endothelial cell–derived EVs at days 10.5 p.c. and 11.5 p.c. Representative images (A) of uterus (top), placenta (middle), and embryo (bottom) and bar graphs quantifying (B) embryonic survival, (C) embryonic height, and (D) placental diameter. Size bar represents 1 mm. (E-F) Altered placental morphology after EV injections. (E) Representative images of placental histology (H&E staining) showing enhanced maternal vascularization (blood lacunae; enucleated erythrocytes) and reduced fetal vascularization (nucleated erythrocytes) after EV injections. (F) Bar graph summarizing quantification of total vascularized area; analyses performed at day 12.5 p.c. Size bar represents 20 µm. (G-L) Characterization of renal pathology in pregnant (Preg) and nonpregnant (Non-Preg) mice following EV injection. Representative images showing enhanced renal pathology in pregnant mice after EV injections, characterized by enlarged glomeruli (G, PAS staining, top; H, bar graph reflecting quantification) and podocyte effacement and thickened glomerular basement membrane (GBM) (G, TEM, n = 3, bottom; I, bar graph reflecting glomerular basement membrane thickness). Proteinuria is increased in EV-injected pregnant mothers at day 12.5 p.c. (J, bar graph summarizing data of P/C ratio). These features of renal dysfunction are not observed in EV-injected nonpregnant females. Size bar represents 15 µm for PAS staining and 1 µm for TEM images, respectively. (K) Elevated blood pressure in EV-injected pregnant mice at day 12.5 p.c. EVs have no impact on blood pressure in nonpregnant mice; bar graph summarizing results. (L) sFlt-1 plasma levels. The PE marker sFlt-1 is increased in blood samples obtained from EV-injected pregnant mice as compared with controls (bar graph summarizing results). Data shown represent mean ± SEM of at least 8 placentae or embryos analyzed from at least 3 different litters of each group or 5 pregnant females per group. Control mice (C) were injected with the supernatant obtained after the last PBS wash during EV isolation. *P < .05, **P < .01. (B-D, H-K) Student t test; (F) ANOVA. Dias, diastolic; ns, nonsignificant; Sys, systolic.

EVs impair embryonic and placental development and cause a PE-like phenotype in mice. (A-D) Impaired pregnancy outcome in C57BL/6 mice at day 12.5 p.c. following IV injection of mouse endothelial cell–derived EVs at days 10.5 p.c. and 11.5 p.c. Representative images (A) of uterus (top), placenta (middle), and embryo (bottom) and bar graphs quantifying (B) embryonic survival, (C) embryonic height, and (D) placental diameter. Size bar represents 1 mm. (E-F) Altered placental morphology after EV injections. (E) Representative images of placental histology (H&E staining) showing enhanced maternal vascularization (blood lacunae; enucleated erythrocytes) and reduced fetal vascularization (nucleated erythrocytes) after EV injections. (F) Bar graph summarizing quantification of total vascularized area; analyses performed at day 12.5 p.c. Size bar represents 20 µm. (G-L) Characterization of renal pathology in pregnant (Preg) and nonpregnant (Non-Preg) mice following EV injection. Representative images showing enhanced renal pathology in pregnant mice after EV injections, characterized by enlarged glomeruli (G, PAS staining, top; H, bar graph reflecting quantification) and podocyte effacement and thickened glomerular basement membrane (GBM) (G, TEM, n = 3, bottom; I, bar graph reflecting glomerular basement membrane thickness). Proteinuria is increased in EV-injected pregnant mothers at day 12.5 p.c. (J, bar graph summarizing data of P/C ratio). These features of renal dysfunction are not observed in EV-injected nonpregnant females. Size bar represents 15 µm for PAS staining and 1 µm for TEM images, respectively. (K) Elevated blood pressure in EV-injected pregnant mice at day 12.5 p.c. EVs have no impact on blood pressure in nonpregnant mice; bar graph summarizing results. (L) sFlt-1 plasma levels. The PE marker sFlt-1 is increased in blood samples obtained from EV-injected pregnant mice as compared with controls (bar graph summarizing results). Data shown represent mean ± SEM of at least 8 placentae or embryos analyzed from at least 3 different litters of each group or 5 pregnant females per group. Control mice (C) were injected with the supernatant obtained after the last PBS wash during EV isolation. *P < .05, **P < .01. (B-D, H-K) Student t test; (F) ANOVA. Dias, diastolic; ns, nonsignificant; Sys, systolic.

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