Pregnancies in Diabetes and Obesity: The Capacity-Load Model of Placental Adaptation

Overview

Journal Diabetes

Specialty Endocrinology

Date 2021 Mar 20

PMID 33741605

Citations 15

Authors

Gernot Desoye

Jonathan C K Wells

Affiliations

Soon will be listed here.

Abstract

Excess nutritional supply to the growing fetus, resulting from maternal diabetes and obesity, is associated with increased risks of fetal maldevelopment and adverse metabolic conditions in postnatal life. The placenta, interposed between mother and fetus, serves as the gateway between the two circulations and is usually considered to mediate maternal exposures to the fetus through a direct supply line. In this Perspective, however, we argue that the placenta is not an innocent bystander and mounts responses to fetal "signals of distress" to sustain its own adequate function and protect the fetus. We describe several types of protection that the placenta can offer the fetus against maternal metabolic perturbations and offer a theoretical model of how the placenta responds to the intrauterine environment in maternal diabetes and obesity to stabilize the fetal environment. Our approach supports growing calls for early screening and control of pregnancy metabolism to minimize harmful fetal outcomes.

Citing Articles

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Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study.

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Obesity-associated non-oxidative genotoxic stress alters trophoblast turnover in human first-trimester placentas.

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References

Cnattingius S, Villamor E, Lagerros Y, Wikstrom A, Granath F . High birth weight and obesity--a vicious circle across generations. Int J Obes (Lond). 2011; 36(10):1320-4. DOI: 10.1038/ijo.2011.248. View

Wells J . Natural selection and sex differences in morbidity and mortality in early life. J Theor Biol. 2000; 202(1):65-76. DOI: 10.1006/jtbi.1999.1044. View

Napoli C, DArmiento F, Mancini F, Postiglione A, Witztum J, Palumbo G . Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest. 1998; 100(11):2680-90. PMC: 508471. DOI: 10.1172/JCI119813. View

Desoye G . The Human Placenta in Diabetes and Obesity: Friend or Foe? The 2017 Norbert Freinkel Award Lecture. Diabetes Care. 2018; 41(7):1362-1369. DOI: 10.2337/dci17-0045. View

Cvitic S, Longtine M, Hackl H, Wagner K, Nelson M, Desoye G . The human placental sexome differs between trophoblast epithelium and villous vessel endothelium. PLoS One. 2013; 8(10):e79233. PMC: 3812163. DOI: 10.1371/journal.pone.0079233. View

Petry C, Wobken J, McKay H, Eaton M, Seybold V, Johnson D . Placental transferrin receptor in diabetic pregnancies with increased fetal iron demand. Am J Physiol. 1994; 267(4 Pt 1):E507-14. DOI: 10.1152/ajpendo.1994.267.4.E507. View

Lang I, Pabst M, Hiden U, Blaschitz A, Dohr G, Hahn T . Heterogeneity of microvascular endothelial cells isolated from human term placenta and macrovascular umbilical vein endothelial cells. Eur J Cell Biol. 2003; 82(4):163-73. DOI: 10.1078/0171-9335-00306. View

Di Renzo G, Rosati A, Sarti R, Cruciani L, Cutuli A . Does fetal sex affect pregnancy outcome?. Gend Med. 2007; 4(1):19-30. DOI: 10.1016/s1550-8579(07)80004-0. View

Walsh J, Segurado R, Mahony R, Foley M, McAuliffe F . The Effects of Fetal Gender on Maternal and Fetal Insulin Resistance. PLoS One. 2015; 10(9):e0137215. PMC: 4569192. DOI: 10.1371/journal.pone.0137215. View

10.

Hemachandra A, Klebanoff M . Use of serial ultrasound to identify periods of fetal growth restriction in relation to neonatal anthropometry. Am J Hum Biol. 2006; 18(6):791-7. DOI: 10.1002/ajhb.20552. View

11.

Heijmans B, Tobi E, Stein A, Putter H, Blauw G, Susser E . Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105(44):17046-9. PMC: 2579375. DOI: 10.1073/pnas.0806560105. View

12.

Powe C, Kwak S . Genetic Studies of Gestational Diabetes and Glucose Metabolism in Pregnancy. Curr Diab Rep. 2020; 20(12):69. PMC: 8132191. DOI: 10.1007/s11892-020-01355-3. View

13.

Eder M, Csapo B, Wadsack C, Haas J, Catalano P, Desoye G . Sex differences in the association of cord blood insulin with subcutaneous adipose tissue in neonates. Int J Obes (Lond). 2015; 40(3):538-42. DOI: 10.1038/ijo.2015.185. View

14.

Sun Y, Kopp S, Strutz J, Gali C, Zandl-Lang M, Fanaee-Danesh E . Gestational diabetes mellitus modulates cholesterol homeostasis in human fetoplacental endothelium. Biochim Biophys Acta Mol Cell Biol Lipids. 2018; 1863(9):968-979. DOI: 10.1016/j.bbalip.2018.05.005. View

15.

Lassance L, Miedl H, Absenger M, Diaz-Perez F, Lang U, Desoye G . Hyperinsulinemia stimulates angiogenesis of human fetoplacental endothelial cells: a possible role of insulin in placental hypervascularization in diabetes mellitus. J Clin Endocrinol Metab. 2013; 98(9):E1438-47. DOI: 10.1210/jc.2013-1210. View

16.

Hirschmugl B, Crozier S, Matthews N, Kitzinger E, Klymiuk I, Inskip H . Relation of placental alkaline phosphatase expression in human term placenta with maternal and offspring fat mass. Int J Obes (Lond). 2018; 42(6):1202-1210. PMC: 6173293. DOI: 10.1038/s41366-018-0136-8. View

17.

Scholler M, Wadsack C, Metso J, Chirackal Manavalan A, Sreckovic I, Schweinzer C . Phospholipid transfer protein is differentially expressed in human arterial and venous placental endothelial cells and enhances cholesterol efflux to fetal HDL. J Clin Endocrinol Metab. 2012; 97(7):2466-74. DOI: 10.1210/jc.2011-2969. View

18.

McIntyre D, Desoye G, Dunne F, Simeoni U, H A Visser G, Kapur A . FIGO analysis of research priorities in hyperglycemia in pregnancy. Diabetes Res Clin Pract. 2018; 145:5-14. DOI: 10.1016/j.diabres.2018.03.026. View

19.

Mitanchez D, Chavatte-Palmer P . Review shows that maternal obesity induces serious adverse neonatal effects and is associated with childhood obesity in their offspring. Acta Paediatr. 2018; 107(7):1156-1165. DOI: 10.1111/apa.14269. View

20.

Gauster M, Desoye G, Totsch M, Hiden U . The placenta and gestational diabetes mellitus. Curr Diab Rep. 2011; 12(1):16-23. DOI: 10.1007/s11892-011-0244-5. View