Uteroplacental Glucose Uptake and Fetal Glucose Consumption: A Quantitative Study in Human Pregnancies.

Context: Maternal glucose levels and body mass index (BMI) are determinants of fetal overgrowth, but their relation to fetal glucose consumption is not well characterized in human pregnancy. Objectives: To quantify uteroplacental glucose uptake and the allocation of glucose between the placenta and fetus and to identify factors that affect fetal glucose consumption. Design: Human in vivo study in term pregnancies. Setting: Oslo University Hospital, Norway. Participants: One hundred seventy-nine healthy women with elective cesarean section. Interventions: Uterine and umbilical blood flow was determined using Doppler ultrasonography. Glucose and insulin were measured in the maternal radial artery and uterine vein and the umbilical artery and vein. In a subcohort (n = 33), GLUT1 expression was determined in isolated syncytiotrophoblast basal and microvillous plasma membranes. Main Outcome Measures: Uteroplacental glucose uptake and placental and fetal glucose consumption quantified by the Fick principle. Results: Median (Q1, Q3) uteroplacental glucose uptake was 117.1 (59.1, 224.9) µmol⋅min-1, and fetal and placental glucose consumptions were 28.9 (15.4, 41.8) µmol⋅min-1⋅kg fetus-1 and 51.4 (-65.8, 185.4) µmol⋅min-1⋅kg placenta-1, respectively. Fetal glucose consumption correlated with birth weight (ρ: 0.34; P < 0.001) and maternal-fetal glucose gradient (ρ: 0.60; P < 0.001), but not with maternal BMI or uteroplacental glucose uptake. Uteroplacental glucose uptake was correlated to placental glucose consumption (ρ: 0.77; P < 0.001). Fetal and placental glucose consumptions were inversely correlated (ρ: -0.47; P < 0.001), but neither was correlated with placental GLUT1 expression. Conclusion: These findings suggest that fetal glucose consumption is balanced against the placental needs for glucose and that placental glucose consumption is a key modulator of maternal-fetal glucose transfer in women.

The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.