Placental Regulation of Energy Homeostasis During Human Pregnancy

Abstract

Successful pregnancies rely on sufficient energy and nutrient supply, which require the mother to metabolically adapt to support fetal needs. The placenta has a critical role in this process, as this specialized organ produces hormones and peptides that regulate fetal and maternal metabolism. The ability for the mother to metabolically adapt to support the fetus depends on maternal prepregnancy health. Two-thirds of pregnancies in the United States involve obese or overweight women at the time of conception. This poses significant risks for the infant and mother by disrupting metabolic changes that would normally occur during pregnancy. Despite well characterized functions of placental hormones, there is scarce knowledge surrounding placental endocrine regulation of maternal metabolic trends in pathological pregnancies. In this review, we discuss current efforts to close this gap of knowledge and highlight areas where more research is needed. As the intrauterine environment predetermines the health and wellbeing of the offspring in later life, adequate metabolic control is essential for a successful pregnancy outcome. Understanding how placental hormones contribute to aberrant metabolic adaptations in pathological pregnancies may unveil disease mechanisms and provide methods for better identification and treatment. Studies discussed in this review were identified through PubMed searches between the years of 1966 to the present. We investigated studies of normal pregnancy and metabolic disorders in pregnancy that focused on energy requirements during pregnancy, endocrine regulation of glucose metabolism and insulin resistance, cholesterol and lipid metabolism, and placental hormone regulation.

Keywords: energy homeostasis; gestational diabetes; metabolism; placenta; pregnancy.

Figure 1.

Fasting plasma glucose levels in normal pregnancy and GDM. In preconception, women who later go on to have normal pregnancies exhibit a mean FPG of 81 mg/dL (12). Mean FPG levels for women with normal pregnancies slightly decrease to 80 mg/dL, 77 mg/dL, and 76 mg/dL in the first, second, and third trimesters, respectively (12). A study by Sesmilo et al showed that first trimester FPG may vary, as their cohort of 6845 women had a mean FPG of 83 with a standard deviation of ± 7.3 mg/dL (132). Of these women, 10.2% developed GDM, which showed that women with a FPG ≥ 88 mg/dL in the first trimester were 1.82 times more likely to be diagnosed with GDM in the second trimester (132). Gestational diabetes mellitus is diagnosed in the first or second trimester if the patient measures a FPG ≥ 92 mg/dL by the 1-step OGTT (99). In a study by Seabra et al, they showed that GDM patients had a significantly higher FPG (90 mg/dL) compared to women without pregnancy complications (FPG 77.8 mg/dL, P = 0.016) in the third trimester (133).

Figure 2.

Mean plasma lipid concentrations measured throughout GDM pregnancies. Gestational diabetes mellitus pregnancies often involve abnormal lipid concentrations throughout pregnancy. As well, infants born to mothers with GDM often have increased adipose tissue at birth. Bao et al identified that women with higher triglycerides in early pregnancy have an increased risk of developing GDM in later pregnancy (103). As well, lower HDL cholesterol in early pregnancy significantly increases the risk for developing GDM in later pregnancy (103). Changes in LDL cholesterol or total cholesterol throughout pregnancy was not shown to be significantly associated with risk of developing GDM (103). *P < 0.05 indicates significant differences in HDL, LDL cholesterol, or triglyceride concentration in GDM pregnancies compared to normal pregnancies during that gestation age (103). Image was adapted from Bao et al. Plasma concentrations of lipids during pregnancy and the risk of gestational diabetes mellitus: a longitudinal study. J Diabetes. 2018;10(6):487–495.

Figure 3.

Mean plasma lipid concentrations measured throughout normal pregnancies. Healthy pregnancies typically show HDL cholesterol increases from 60–70 mg/dL in the late first trimester, and these levels decrease to below 60 mg/dL at the end of gestation (103). Low density lipoprotein cholesterol gradually increases across gestation from around 86–126 mg/dL (103). Triglycerides increase in the beginning of the second trimester, from around 130 mg/dL, and increase until the end of gestation to approximately 280 mg/dL (103). Total cholesterol increases from approximately 180 mg/dL at the end of the first trimester to around 230 mg/dL at the end of the third trimester (103). Image was adapted from Bao et al. Plasma concentrations of lipids during pregnancy and the risk of gestational diabetes mellitus: a longitudinal study. J Diabetes. 2018;10(6):487–495.

Figure 4.

Leptin measurements in the second trimester of pregnancy. Kautzky-Willer et al showed that there is a significant increase in plasma leptin levels in women who have GDM (24.9 ng/mL) compared to normal pregnancies (18.2 ng/mL) (109). Leptin levels during nonpregnancy are 8.2 ng/mL (109). ***P < 0.001.

Figure 5.

Irisin measurements in the first trimester of pregnancy. Erol et al showed that there is a decrease in irisin levels in women who later developed GDM (452 ng/mL) compared to normal pregnancies (752 ng/mL) (121). ***P < 0.001.