Circulating and utero-placental adaptations to chronic placental ischemia in the rat.
ABSTRACT While utero-placental insufficiency is associated with adverse outcomes for both mother and fetus, many of the maternal-fetal adaptations during pregnancy in models of fetal compromise remain unclear. The purpose of this study was to determine if chronically reduced uterine perfusion pressure (RUPP) during days 14-19 of gestation alters feto-placental growth differentially from the cervical to ovarian ends of the uterus and generates metabolic adaptations such as increased blood lactate (BLa) concentrations and lactate transporter expression in the placenta. Fetal growth restriction was evident, placental efficiency (fetal weight/placental weight) decreased (4.7 ± 0.35 vs. 5.9 ± 0.30; P < 0.05) and fetal growth pattern within the uterus was altered in the RUPP compared to the normal pregnant (NP) rats. Blood lactate concentrations were increased (3.3 ± 0.3 vs. 2.1 ± 0.4 mmol/l; P < 0.05) in NP compared to virgin rats, and in RUPP compared to NP (5.0 ± 0.6 vs. 3.3 ± 0.3 mmol/l; P < 0.05). Lactate concentration was increased (10.0 ± 0.6 vs. 7.1 ± 0.8 mmol/l; P < 0.05) in the media from hypoxic compared to normoxic BeWo cells. No changes in expression of placental MCT1, 2, or 4 were observed between RUPP and NP rats. RUPP resulted in decreased plasma leptin (2.0 ± 0.3 vs. 3.1 ± 0.4; P < 0.05) but no change in IGF-1 compared to NP. The present data indicate chronic placental ischemia results in numerous endocrine and metabolic changes during late pregnancy in the rat and that the RUPP model has differential effects on fetal growth depending on uterine position.