Figure 4
Figure 4. Pravastatin prevents pregnancy loss in CBA/J × DBA/2 mice. (A,B) CBA/J × DBA/2 and CBA/J × BALB/c mice were treated with pravastatin (P) (n = 5-7). Mice were killed on day 15 of pregnancy, uteri were dissected, and fetal resorption frequency was calculated. (A) Treatment with P prevented fetal loss (*P < .005, CBA/J × DBA/2 versus CBA/J × DBA/2 plus P). (B) P also prevented IUGR in CBA/J × DBA/2 mice (*P < .01, CBA/J × DBA/2 versus CBA/J × DBA/2 plus P). (C) Litter size at birth. P increased the litter size in CBA/J × DBA/2 mice. (D) Superoxide generation, and TF and fibrin staining in day-15 placentas. Increased free radical–mediated lipid peroxidation was observed in placentas from CBA/J × DBA/2 mice (i). No signs of oxidative damage were observed in placentas of CBA/J × DBA/2 mice that received P (ii). Extensive TF (iii) and fibrin (v) staining (brown color) was found in placentas from CBA/J × DBA/2 mice. In contrast, CBA/J × DBA/2 mice treated with P showed minimal and diffuse TF (iv) and fibrin staining (vi) in the placentas. Original magnification ×100. (E) Serum total nitric oxide (NO) production. In control CBA/J × BALB/c matings, NO levels increase along pregnancy. In contrast, in CBA/J × DBA/2 mice NO levels diminish as pregnancy progresses. P treatment restores NO levels to values comparable with those observed in CBA/J × BALB/c. (F) Placental perfusion studies. In placentas from CBA/J × DBA/2 mice treated with P, as in control matings (Figure 1Ci) with normal pregnancies, the fluorescent tracer accumulated in the placental labyrinth showing an adequate blood perfusion (n = 5-6). (G) FACS analysis of TF in peripheral blood monocytes. Increased TF-positive monocytes were observed in CBA/J × DBA/2 matings. P inhibited increased TF expression on monocytes. (H) TF staining and superoxide production in SM9-1 trophoblasts. Increased TF staining (i) and superoxide production (iii) were observed in SM9-1 cells incubated with 8000 pg/mL sFlt-1. In contrast, addition of P 3 hours prior to sFlt-1 incubation prevented TF expression (ii) and superoxide generation (iv) (n = 5-7 experiments/group). Data are mean values plus or minus SD.

Pravastatin prevents pregnancy loss in CBA/J × DBA/2 mice. (A,B) CBA/J × DBA/2 and CBA/J × BALB/c mice were treated with pravastatin (P) (n = 5-7). Mice were killed on day 15 of pregnancy, uteri were dissected, and fetal resorption frequency was calculated. (A) Treatment with P prevented fetal loss (*P < .005, CBA/J × DBA/2 versus CBA/J × DBA/2 plus P). (B) P also prevented IUGR in CBA/J × DBA/2 mice (*P < .01, CBA/J × DBA/2 versus CBA/J × DBA/2 plus P). (C) Litter size at birth. P increased the litter size in CBA/J × DBA/2 mice. (D) Superoxide generation, and TF and fibrin staining in day-15 placentas. Increased free radical–mediated lipid peroxidation was observed in placentas from CBA/J × DBA/2 mice (i). No signs of oxidative damage were observed in placentas of CBA/J × DBA/2 mice that received P (ii). Extensive TF (iii) and fibrin (v) staining (brown color) was found in placentas from CBA/J × DBA/2 mice. In contrast, CBA/J × DBA/2 mice treated with P showed minimal and diffuse TF (iv) and fibrin staining (vi) in the placentas. Original magnification ×100. (E) Serum total nitric oxide (NO) production. In control CBA/J × BALB/c matings, NO levels increase along pregnancy. In contrast, in CBA/J × DBA/2 mice NO levels diminish as pregnancy progresses. P treatment restores NO levels to values comparable with those observed in CBA/J × BALB/c. (F) Placental perfusion studies. In placentas from CBA/J × DBA/2 mice treated with P, as in control matings (Figure 1Ci) with normal pregnancies, the fluorescent tracer accumulated in the placental labyrinth showing an adequate blood perfusion (n = 5-6). (G) FACS analysis of TF in peripheral blood monocytes. Increased TF-positive monocytes were observed in CBA/J × DBA/2 matings. P inhibited increased TF expression on monocytes. (H) TF staining and superoxide production in SM9-1 trophoblasts. Increased TF staining (i) and superoxide production (iii) were observed in SM9-1 cells incubated with 8000 pg/mL sFlt-1. In contrast, addition of P 3 hours prior to sFlt-1 incubation prevented TF expression (ii) and superoxide generation (iv) (n = 5-7 experiments/group). Data are mean values plus or minus SD.

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