Angiotensin-Converting Enzyme 2 Deficiency Is Associated With Impaired Gestational Weight Gain and Fetal Growth Restriction

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system that influences the relative expression of angiotensin II (Ang II) and Ang-(1-7). Although ACE2 expression increases in normal pregnancy, the impact of ACE2 deficiency in pregnancy has not been elucidated. We determined the influence of ACE2 deficiency on circulating and tissue renin-angiotensin system components, fetal and maternal growth characteristics, and maternal hemodynamics (mean blood pressure and cardiac output) at day 18 of gestation. Gestational body weight gain was lower in the ACE2 knockout (KO) versus C57BL/6 (wild-type) mice (30.3±4.7 versus 38.2±1.0 g; P <0.001). Fetal weight (0.94±0.1 versus 1.24±0.01 g; P <0.01) and length (19.6±0.2 versus 22.2±0.2 mm; P <0.001) were less in KO. Mean blood pressure was significantly reduced in C57BL/6 with pregnancy; it was elevated ( P <0.05) in the KO virgin and pregnant mice, and this was associated with an increased cardiac output in both C57BL/6 and KO pregnant mice ( P <0.05). Plasma Ang-(1-7) was reduced in pregnant KO mice ( P <0.05). Placenta Ang II levels were higher in KO mice (52.9±6.0 versus 22.0±3.3 fmol/mg of protein; P <0.001). Renal Ang II levels were greater in KO virgin mice (30.0±1.7 versus 23.7±1.1 fmol/mg of protein; P <0.001). There was no change in the Ang-(1-7) levels in the KO placenta and virgin kidney. These results suggest that ACE2 deficiency and associated elevated placenta Ang II levels impact pregnancy by impairing gestational weight gain and restricting fetal growth.