Maternal insulin-like growth factor 1 and 2 differentially affect the renin–angiotensin system during pregnancy in the guinea pig

摘要: Abstract Objective Insulin-like growth factors (IGFs) are known to interact with the renin–angiotensin system (RAS). We previously demonstrated that administration of IGF1 guinea pigs in early mid pregnancy promotes placental function and fetal late gestation. Early IGF2 had sustained, but not acute, effects on these parameters also structural differentiation. Here, we aimed determine whether IGFs RAS gestation modulate development increase survival, if binding IGF2R is implicated sustained treatment. Design At day 20 pregnancy, were infused 1mg/kg/day IGF1, IGF2, Leu27 or vehicle for 18days sacrificed either 62 (late pregnancy) during infusion period 35 (early–mid pregnancy). Placental structure at was analyzed using morphometric technique expression genes placenta plasma renin activity measured both time points. Results Compared gestation, reduced total midsagittal cross-sectional area (−17%, p =0.02) labyrinth (−22%, =0.014) did alter volume nor labyrinth:interlobium ratios. treatment affect structure. mRNA any quantified ( AGTR1, ACE, AGT, TGFB1 ) increased by more than 16-fold =0.005) 62. AGTR1 (+88%, =0.03) decreased AGT (−73%, =0.01) compared vehicle-treated group 35, 9-fold =0.016) 6-fold =0.019) respectively. Both ratio active:total protein (+22% =0.026 =0.038) 62, IGF2-treated mothers showed a marked (+495%) active (+359%) 41% =0.042). animals higher levels (+73%, =0.001) (+71%, control. Conclusions The data obtained current study suggest potential alternate roles induction after IGF 2 treatments activation prorenin placenta, possibly due protease activity. In addition, may enhance maternal adaptation through stimulation kidney. differentiation therapeutic exogenous improving outcomes.