Placental and vascular adaptations to exercise training before and during pregnancy in the rat

Abstract

Although exercise during pregnancy is generally recommended and thought to be beneficial to mother and fetus, the nature of the adaptations to exercise during pregnancy and how they may be beneficial remain poorly understood. Recent studies suggest that exercise may stimulate expression of several cytoprotective and pro-angiogenic molecules such as heat shock proteins (HSP) and vascular endothelial growth factors (VEGF). We hypothesized that exercise training during pregnancy improves angiogenic balance, increases HSP expression, and improves endothelial function. Female rats were given access to an exercise wheel for 6 wk before and during pregnancy. On day 19 of pregnancy tissues were collected and snap frozen for later analysis. Western blots were performed in skeletal muscle and placenta. HSP 27 (3.7 ± 0.36 vs. 2.2 ± 0.38; P < 0.05), HSP 60 (2.2 ± 0.73 vs. 0.49 ± 0.08; P < 0.05), and HSP 90 (0.33 ± 0.09 vs. 0.11 ± 0.02; P < 0.05) were increased in the placentas of exercise-trained rats compared with sedentary controls. In addition, exercise training increased (P < 0.05) plasma free VEGF and augmented (P < 0.05) endothelium-dependent vascular relaxation compared with nonexercise control rats. The present data indicates chronic exercise training stimulates HSP expression in the placenta and that regular exercise training increases circulating VEGF in pregnant but not in nonpregnant rats. Although the present findings suggest that exercise before and during pregnancy may promote the expression of molecules that could attenuate placental and vascular dysfunction in complicated pregnancies, further studies are needed to determine the safety and effectiveness of exercise training as a therapeutic modality in pregnancy.

Fig. 1.

Average daily distance run by rats. The distance run by the rats was consistent between the prepregnancy period and the first 2 wk of gestation. The distance run by the pregnant rats decreased in the final week of pregnancy. Data are expressed as means ± SE. Lowercase letters that are different represent P < 0.05.

Fig. 2.

Effects of exercise on hindlimb skeletal muscle expression of ATP synthase (A) and PGC1-α (B). Expression of ATP synthase (A) and PGC1-α (B) were increased in the gastrocnemius muscle of the exercise-trained pregnant rats compared with the nonexercised pregnancy rats. Data are expressed as means ± SE, *P < 0.05.

Fig. 3.

Effects of exercise on placental weight (A) and placental efficiency (B). Placental weight was decreased in the exercise-trained compared with the nonexercised rats, while placental efficiency was increased in the exercise-trained rats. Data are expressed as means ± SE, *P < 0.05.

Fig. 4.

Effects of chronic exercise training on heat shock protein (HSP) 27 expression in placenta. Exercise training before and during pregnancy increased placental expression of HSP27 relative to β-actin. Data are expressed as means ± SE, *P < 0.05.

Fig. 5.

Effects of chronic exercise training on HSP 60 expression in placenta. Chronic exercise training before and during pregnancy increased placental expression of HSP 60 relative to β-actin. Data are expressed as means ± SE, *P < 0.05.

Fig. 6.

Effects of chronic exercise training on HSP 90 expression in placenta. Chronic exercise training before and during pregnancy increased placental expression of HSP 90 relative to β-actin. Data are expressed as means ± SE, *P < 0.05.

Fig. 7.

Endothelial function in late gestation. Wire myography revealed that vessel relaxation to acetylcholine (ACh) (after preconstruction with U41669) was increased in mesenteric vessels of the exercise-trained pregnant rats compared with pregnant rats in the nonexercise group. Data are expressed as mean percent relaxation to each dose of ACh ± SE, *P < 0.05.

Fig. 8.

Circulating vascular endothelial growth factor (VEGF) and angiogenic balance in late gestation. Circulating VEGF (A) was increased in the exercise-trained rats compared with the nonexercised group, while VEGF levels in age-matched virgin rats were unchanged by exercise training. B: angiogenic balance (sFlt-1:VEGF) was improved (i.e., decreased) by exercise training in pregnancy. Data are expressed as means ± SE, *P < 0.05.