LAUSR

Preeclampsia (PreE), or gestational hypertension (GH) concurrent with proteinuria, is a leading cause of maternal and fetal mortality worldwide. PreE often leads to fetal growth restriction resulting in low birth weight offspring. Low birth weight infants are at higher risk of developing cardiovascular disease later in life. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus ) develops spontaneous GH with proteinuria and fetal growth restriction. We hypothesize that GH will developmentally program offspring to reduced kidney function and metabolic disease. Maternal systolic arterial pressure (SAP) was measured via forearm plethysmography prior to pregnancy and during the 3 rd trimester of pregnancy. At 1-3 years of age, offspring were single-housed for water intake and urine flow rate collections followed by blood pressure measurement and venous blood sampling. Animals were grouped by pregnancy phenotype. SAP for normotensive (NT, n=23) mothers did not change in pregnancy, but increased during third trimester for GH (Δ=35 ± 7 mmHg, n=34). NT pregnancies resulted in a 4% stillbirth rate (1/23) compared with 29% in GH (10/34). Surviving GH offspring had reduced birth weight (NT 336 ± 11g vs. GH 295 ± 8g, p<0.05). Fasting glucose was higher in progeny born to GH pregnancies (NT 69 ± 8 mg/dl, n=13; GH 92 ± 6 mg/dl, n=20). Urinary protein excretion was higher in offspring born to GH pregnancies (NT 152 ± 27 mg/day; GH 318 ± 46 mg/day). SAP of offspring was similar between maternal phenotype (NT 107 ± 8 mmHg; GH 109 ± 5 mmHg). Juvenile SAP was unrelated to fasting glucose or urinary protein excretion, indicating that these factors are determined by maternal SAP during pregnancy, rather than juvenile phenotype. Thus, GH is associated with fetal growth restriction in the form of high stillbirth rates and lower surviving-offspring birth weights in the AGM. GH offspring have elevated fasting glucose and possible decreased kidney function as evidenced by proteinuria. GH could be programming offspring for early life metabolic risk factors and declining renal function. Future studies include oral glucose tolerance tests and additional markers of renal dysfunction to further assess in utero programming of the pathogenesis of cardiovascular and metabolic disease.