Adolescent Offspring of Preeclamptic Nonhuman Primate Mothers Have Impaired Glucose Tolerance and Proteinuria
Authors: Sickles Shea , Weaver Chelsea , Taylor Jessica , Osborn Jeffrey 
Published: April 2020

Hypertensive pregnancy disorders are the most common pregnancy complication and are a primary cause of maternal and fetal mortality worldwide. Preeclampsia (PE), defined as de novo maternal hypertension and proteinuria in the 2nd or 3rd trimester, is associated with preterm birth and long‐term cardiovascular risk in both mothers and offspring. The African Green Monkey (AGM; Chlorocebus aethiops sabaeus) develops spontaneous preeclampsia and exhibits fetal growth restriction. We hypothesize that PE pregnancies leading to reduced birthweight may increase the risk for impaired renal and metabolic function in offspring. Offspring of normotensive (NT) pregnancies averaged 335.6 ± 9.6g birthweight, while birthweight of offspring born to PE females was 299.4 ± 9.0g, indicating fetal growth restriction (NT n=12; PE n=24; pδ0.05). To assess glucose tolerance, an oral glucose tolerance test (OGTT) was conducted on a subset of offspring at 1–3 years of age. Glucose was fed to a final concentration of 1.75 g/kg bodyweight. Blood glucose was measured by finger stick with standard glucometry prior to the glucose load and at 15, 30, 60, 90, and 120 minutes post glucose load. Fasting blood glucose was similar between NT and PE juveniles (NT n=9, 77.7 ± 8.4 mg/dl; PE n=11, 82.2 ± 7.6 mg/dl; p>0.05). Blood glucose of NT juveniles peaked at 15 minutes (141.7 ± 18.9mg/dl) and subsequently decreased. In contrast, PE juveniles showed a biphasic glucose response, first peaking at 15 minutes (132 ± 13 mg/dl) and again at 60 minutes (149.4 ± 14.1 mg/dl). The area under the curve of the OGTT was used as an index of glucose tolerance. Glucose tolerance of PE juveniles was impaired compared to NT juveniles (NT n=9, 10994 ± 1390 min*mg/dl; PE n=11, 14831 ± 5761 min*mg/dl; pδ0.05). To monitor water intake and urine flow, juveniles were individually housed (NT n=9; PE n=10). After an acclimation period of 1 week, water intake and urine flow were measured for 3 consecutive days. Urinary protein excretion was greater in PE offspring (NT 152.0 ± 61.7 mg/day vs. PE 354.7 ± 55.8 mg/day; pδ0.05). Sodium excretion was similar between groups (NT 16.10 ± 3.2 mmol/day; PE 18.96 ± 2.9 mmol/day; p>0.05). However, potassium excretion was greater in PE offspring (6.19 ± 0.8 mmol/day vs. NT 2.70 ± 0.9 mmol/day; pδ0.05). Plasma creatinine was similar between offspring of NT and PE females (NT 1.74 ± 0.2 mg/dl; PE 1.65 ± 0.1 mg/dl; p>0.05). An individual with the lowest birth weight of the PE cohort (228.5g vs. mean 314.1 ± 14g) had the highest creatinine level (2.38 mg/dl vs. mean 1.65 ± 0.1 mg/dl) and elevated protein excretion (504.6 mg/day vs. mean 378.5 ± 74.7 mg/day). PE in AGMs is associated with fetal growth restriction resulting in low birthweights. Juveniles born to PE females showed impaired glucose tolerance, proteinuria, and kaliuresis. Exposure to PE in utero may predispose offspring to impaired renal and metabolic function in early adolescence. Continued monitoring of current PE juveniles and phenotyping of 2019 offspring will further assess the influence of maternal pregnancy phenotype on adolescent markers of renal and metabolic impairment.

Support or Funding Information

This work was supported by research funds from Primate Plus, LLC.