Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

Author(s): Samantha Bedell, Janine Hutson, Barbra de Vrijer*, Genevieve Eastabrook

Journal Name: Current Vascular Pharmacology

Volume 19 , Issue 2 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

Keywords: Placenta, obesity, gestational diabetes mellitus, vascular development, transport, metabolism.

Burton GJ, Fowden AL, Thornburg KL. Placental origins of chronic disease. Physiol Rev 2016; 96(4): 1509-65.
[http://dx.doi.org/10.1152/physrev.00029.2015] [PMID: 27604528]
Sandovici I, Hoelle K, Angiolini E, Constância M. Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming. Reprod Biomed Online 2012; 25(1): 68-89.
[http://dx.doi.org/10.1016/j.rbmo.2012.03.017] [PMID: 22560117]
Mitchell S, Shaw D. The worldwide epidemic of female obesity. Best Pract Res Clin Obstet Gynaecol 2015; 29(3): 289-99.
[http://dx.doi.org/10.1016/j.bpobgyn.2014.10.002] [PMID: 25487257]
Saben J, Lindsey F, Zhong Y, et al. Maternal obesity is associated with a lipotoxic placental environment. Placenta 2014; 35(3): 171-7.
[http://dx.doi.org/10.1016/j.placenta.2014.01.003] [PMID: 24484739]
Guariguata L, Linnenkamp U, Beagley J, Whiting DR, Cho NH. Global estimates of the prevalence of hyperglycaemia in pregnancy. Diabetes Res Clin Pract 2014; 103(2): 176-85.
[http://dx.doi.org/10.1016/j.diabres.2013.11.003] [PMID: 24300020]
Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The pathophysiology of gestational diabetes mellitus. Int J Mol Sci 2018; 19(11)E3342
[http://dx.doi.org/10.3390/ijms19113342] [PMID: 30373146]
Jayabalan N, Nair S, Nuzhat Z, et al. Cross talk between adipose tissue and placenta in obese and gestational diabetes mellitus pregnancies via exosomes. Front Endocrinol (Lausanne) 2017; 8: 239.
[http://dx.doi.org/10.3389/fendo.2017.00239] [PMID: 29021781]
Prince CS, Maloyan A, Myatt L. Maternal obesity alters brain derived neurotrophic factor (BDNF) signaling in the placenta in a sexually dimorphic manner. Placenta 2017; 49: 55-63.
[http://dx.doi.org/10.1016/j.placenta.2016.11.010] [PMID: 28012455]
Pantham P, Aye IL, Powell TL. Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 2015; 36(7): 709-15.
[http://dx.doi.org/10.1016/j.placenta.2015.04.006] [PMID: 25972077]
Gaillard R. Maternal obesity during pregnancy and cardiovascular development and disease in the offspring. Eur J Epidemiol 2015; 30(11): 1141-52.
[http://dx.doi.org/10.1007/s10654-015-0085-7] [PMID: 26377700]
Kim SY, England L, Wilson HG, Bish C, Satten GA, Dietz P. Percentage of gestational diabetes mellitus attributable to overweight and obesity. Am J Public Health 2010; 100(6): 1047-52.
[http://dx.doi.org/10.2105/AJPH.2009.172890] [PMID: 20395581]
Catalano PM, McIntyre HD, Cruickshank JK, et al. The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes. Diabetes Care 2012; 35(4): 780-6.
[http://dx.doi.org/10.2337/dc11-1790] [PMID: 22357187]
Gallo LA, Barrett HL, Dekker Nitert M. Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes. Placenta 2017; 54: 59-67.
[http://dx.doi.org/10.1016/j.placenta.2016.12.006] [PMID: 27993398]
Coughlan MT, Vervaart PP, Permezel M, Georgiou HM, Rice GE. Altered placental oxidative stress status in gestational diabetes mellitus. Placenta 2004; 25(1): 78-84.
[http://dx.doi.org/10.1016/S0143-4004(03)00183-8] [PMID: 15013642]
Cross JC, Werb Z, Fisher SJ. Implantation and the placenta: key pieces of the development puzzle. Science 1994; 266(5190): 1508-18.
[http://dx.doi.org/10.1126/science.7985020] [PMID: 7985020]
Woods L, Perez-Garcia V, Hemberger M. Regulation of placental development and its impact on fetal growth-new insights from mouse models. Front Endocrinol (Lausanne) 2018; 9: 570.
[http://dx.doi.org/10.3389/fendo.2018.00570] [PMID: 30319550]
Adjaye J, Huntriss J, Herwig R, et al. Primary differentiation in the human blastocyst: comparative molecular portraits of inner cell mass and trophectoderm cells. Stem Cells 2005; 23(10): 1514-25.
[http://dx.doi.org/10.1634/stemcells.2005-0113] [PMID: 16081659]
Kim SM, Kim JS. A review of mechanisms of implantation. Dev Reprod 2017; 21(4): 351-9.
[http://dx.doi.org/10.12717/DR.2017.21.4.351] [PMID: 29359200]
Salamonsen LA, Evans J, Nguyen HP, Edgell TA. The microenvironment of human implantation: Determinant of reproductive success. Am J Reprod Immunol 2016; 75(3): 218-25.
[http://dx.doi.org/10.1111/aji.12450] [PMID: 26661899]
Wang Y, Zhao S. Vascular biology of the placenta Integrated systems physiology: From molecules to function to disease San Rafael. CA: Morgan & Claypool Life Sciences 2010.
Gude NM, Roberts CT, Kalionis B, King RG. Growth and function of the normal human placenta. Thromb Res 2004; 114(5-6): 397-407.
[http://dx.doi.org/10.1016/j.thromres.2004.06.038] [PMID: 15507270]
Tarrade A, Lai Kuen R, Malassiné A, et al. Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta. Lab Invest 2001; 81(9): 1199-211.
[http://dx.doi.org/10.1038/labinvest.3780334] [PMID: 11555668]
Nakashima A, Aoki A, Kusabiraki T, et al. Role of autophagy in oocytogenesis, embryogenesis, implantation, and pathophysiology of pre-eclampsia. J Obstet Gynaecol Res 2017; 43(4): 633-43.
[http://dx.doi.org/10.1111/jog.13292] [PMID: 28418212]
Hayes EK, Tessier DR, Percival ME, et al. Trophoblast invasion and blood vessel remodeling are altered in a rat model of lifelong maternal obesity. Reprod Sci 2014; 21(5): 648-57.
[http://dx.doi.org/10.1177/1933719113508815] [PMID: 24155067]
Bellver J, Ayllón Y, Ferrando M, et al. Female obesity impairs in vitro fertilization outcome without affecting embryo quality. Fertil Steril 2010; 93(2): 447-54.
[http://dx.doi.org/10.1016/j.fertnstert.2008.12.032] [PMID: 19171335]
Comstock IA, Kim S, Behr B, Lathi RB. Increased body mass index negatively impacts blastocyst formation rate in normal responders undergoing in vitro fertilization. J Assist Reprod Genet 2015; 32(9): 1299-304.
[http://dx.doi.org/10.1007/s10815-015-0515-1] [PMID: 26109331]
Monsivais D, Clementi C, Peng J, et al. Bmp7 induces uterine receptivity and blastocyst attachment. Endocrinology 2017; 158(4): 979-92.
[http://dx.doi.org/10.1210/en.2016-1629] [PMID: 28324064]
Schulte MM, Tsai JH, Moley KH. Obesity and PCOS: the effect of metabolic derangements on endometrial receptivity at the time of implantation. Reprod Sci 2015; 22(1): 6-14.
[http://dx.doi.org/10.1177/1933719114561552] [PMID: 25488942]
Li R, Wu J, He J, et al. Mice endometrium receptivity in early pregnancy is impaired by maternal hyperinsulinemia. Mol Med Rep 2017; 15(5): 2503-10.
[http://dx.doi.org/10.3892/mmr.2017.6322] [PMID: 28447735]
Liao S, Vickers MH, Taylor RS, et al. Maternal serum placental growth hormone, insulin-like growth factors and their binding proteins at 20 weeks’ gestation in pregnancies complicated by gestational diabetes mellitus. Hormones (Athens) 2017; 16(3): 282-90.
[http://dx.doi.org/10.1007/BF03401522] [PMID: 29278514]
Babawale MO, Lovat S, Mayhew TM, Lammiman MJ, James DK, Leach L. Effects of gestational diabetes on junctional adhesion molecules in human term placental vasculature. Diabetologia 2000; 43(9): 1185-96.
[http://dx.doi.org/10.1007/s001250051511] [PMID: 11043866]
Cawyer CR, Horvat D, Leonard D, et al. Hyperglycemia impairs cytotrophoblast function via stress signaling. Am J Obstet Gynecol 2014; 211(5): 541.
Groen B, Uuldriks GA, de Vos P, Visser JT, Links TP, Faas MM. Impaired trophoblast invasion and increased numbers of immune cells at day 18 of pregnancy in the mesometrial triangle of type 1 diabetic rats. Placenta 2015; 36(2): 142-9.
[http://dx.doi.org/10.1016/j.placenta.2014.12.004] [PMID: 25555500]
Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ. Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest 1996; 97(2): 540-50.
[http://dx.doi.org/10.1172/JCI118447] [PMID: 8567979]
Li HP, Chen X, Li MQ. Gestational diabetes induces chronic hypoxia stress and excessive inflammatory response in murine placenta. Int J Clin Exp Pathol 2013; 6(4): 650-9.
[PMID: 23573311]
Fernandez-Twinn DS, Gascoin G, Musial B, et al. Exercise rescues obese mothers’ insulin sensitivity, placental hypoxia and male off-spring insulin sensitivity. Sci Rep 2017; 7: 44650.
[http://dx.doi.org/10.1038/srep44650] [PMID: 28291256]
Mihu D, Razvan C, Malutan A, Mihaela C. Evaluation of maternal systemic inflammatory response in preeclampsia. Taiwan J Obstet Gynecol 2015; 54(2): 160-6.
[http://dx.doi.org/10.1016/j.tjog.2014.03.006] [PMID: 25951721]
Bartha JL, Romero-Carmona R, Comino-Delgado R. Inflammatory cytokines in intrauterine growth retardation. Acta Obstet Gynecol Scand 2003; 82(12): 1099-102.
[http://dx.doi.org/10.1046/j.1600-0412.2003.00259.x] [PMID: 14616253]
Cotechini T, Komisarenko M, Sperou A, Macdonald-Goodfellow S, Adams MA, Graham CH. Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia. J Exp Med 2014; 211(1): 165-79.
[http://dx.doi.org/10.1084/jem.20130295] [PMID: 24395887]
Atègbo JM, Grissa O, Yessoufou A, et al. Modulation of adipokines and cytokines in gestational diabetes and macrosomia. J Clin Endocrinol Metab 2006; 91(10): 4137-43.
[http://dx.doi.org/10.1210/jc.2006-0980] [PMID: 16849405]
Challier JC, Basu S, Bintein T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29(3): 274-81.
[http://dx.doi.org/10.1016/j.placenta.2007.12.010] [PMID: 18262644]
Denison FC, Roberts KA, Barr SM, Norman JE. Obesity, pregnancy, inflammation, and vascular function. Reproduction 2010; 140(3): 373-85.
[http://dx.doi.org/10.1530/REP-10-0074] [PMID: 20215337]
Guillemette L, Lacroix M, Battista MC, et al. TNFα dynamics during the oral glucose tolerance test vary according to the level of insulin resistance in pregnant women. J Clin Endocrinol Metab 2014; 99(5): 1862-9.
[http://dx.doi.org/10.1210/jc.2013-4016] [PMID: 24517151]
Bowen JM, Chamley L, Mitchell MD, Keelan JA. Cytokines of the placenta and extra-placental membranes: biosynthesis, secretion and roles in establishment of pregnancy in women. Placenta 2002; 23(4): 239-56.
[http://dx.doi.org/10.1053/plac.2001.0781] [PMID: 11969335]
Jovanović M, Vićovac L. Interleukin-6 stimulates cell migration, invasion and integrin expression in HTR-8/SVneo cell line. Placenta 2009; 30(4): 320-8.
[http://dx.doi.org/10.1016/j.placenta.2009.01.013] [PMID: 19251319]
Wen Z, Chen Y, Long Y, Yu J, Li M. Tumor necrosis factor-alpha suppresses the invasion of HTR-8/SVneo trophoblast cells through microRNA-145-5p-mediated downregulation of Cyr61. Life Sci 2018; 209: 132-9.
[http://dx.doi.org/10.1016/j.lfs.2018.08.005] [PMID: 30081007]
Nakashima A, Yamanaka-Tatematsu M, Fujita N, et al. Impaired autophagy by soluble endoglin, under physiological hypoxia in early pregnant period, is involved in poor placentation in preeclampsia. Autophagy 2013; 9(3): 303-16.
[http://dx.doi.org/10.4161/auto.22927] [PMID: 23321791]
Hung TH, Chen SF, Lo LM, Li MJ, Yeh YL, Hsieh TT. Increased autophagy in placentas of intrauterine growth-restricted pregnancies. PLoS One 2012; 7(7)e40957
[http://dx.doi.org/10.1371/journal.pone.0040957] [PMID: 22815878]
Weiss U, Cervar M, Puerstner P, et al. Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast. Diabetologia 2001; 44(2): 209-19.
[http://dx.doi.org/10.1007/s001250051601] [PMID: 11270678]
Ji L, Chen Z, Xu Y, et al. Systematic characterization of autophagy in gestational diabetes mellitus. Endocrinology 2017; 158(8): 2522-32.
[http://dx.doi.org/10.1210/en.2016-1922] [PMID: 28838138]
Chen DB, Zheng J. Regulation of placental angiogenesis. Microcirculation 2014; 21(1): 15-25.
[http://dx.doi.org/10.1111/micc.12093] [PMID: 23981199]
Acharya G, Sonesson SE, Flo K, Räsänen J, Odibo A. Hemodynamic aspects of normal human feto-placental (umbilical) circulation. Acta Obstet Gynecol Scand 2016; 95(6): 672-82.
[http://dx.doi.org/10.1111/aogs.12919] [PMID: 27130575]
Heinonen S, Taipale P, Saarikoski S. Weights of placentae from small-for-gestational age infants revisited. Placenta 2001; 22(5): 399-404.
[http://dx.doi.org/10.1053/plac.2001.0630] [PMID: 11373149]
Wallace JM, Horgan GW, Bhattacharya S. Placental weight and efficiency in relation to maternal body mass index and the risk of pregnancy complications in women delivering singleton babies. Placenta 2012; 33(8): 611-8.
[http://dx.doi.org/10.1016/j.placenta.2012.05.006] [PMID: 22695104]
Effendi M, Demers S, Giguère Y, et al. Association between first-trimester placental volume and birth weight. Placenta 2014; 35(2): 99-102.
[http://dx.doi.org/10.1016/j.placenta.2013.11.015] [PMID: 24345759]
Hayward CE, Lean S, Sibley CP, et al. Placental adaptation: What can we learn from birthweight:Placental weight ratio? Front Physiol 2016; 7: 28.
[http://dx.doi.org/10.3389/fphys.2016.00028] [PMID: 26903878]
Kovo M, Zion-Saukhanov E, Schreiber L, et al. The effect of maternal obesity on pregnancy outcome in correlation with placental pathology. Reprod Sci 2015; 22(12): 1643-8.
[http://dx.doi.org/10.1177/1933719115592712] [PMID: 26130679]
Taricco E, Radaelli T, Nobile de Santis MS, Cetin I. Foetal and placental weights in relation to maternal characteristics in gestational diabetes. Placenta 2003; 24(4): 343-7.
[http://dx.doi.org/10.1053/plac.2002.0913] [PMID: 12657507]
Martino J, Sebert S, Segura MT, et al. Maternal body weight and gestational diabetes differentially influence placental and pregnancy outcomes. J Clin Endocrinol Metab 2016; 101(1): 59-68.
[http://dx.doi.org/10.1210/jc.2015-2590] [PMID: 26513002]
Gauster M, Desoye G, Tötsch M, Hiden U. The placenta and gestational diabetes mellitus. Curr Diab Rep 2012; 12(1): 16-23.
[http://dx.doi.org/10.1007/s11892-011-0244-5] [PMID: 22102097]
Schwartz N, Quant HS, Sammel MD, Parry S. Macrosomia has its roots in early placental development. Placenta 2014; 35(9): 684-90.
[http://dx.doi.org/10.1016/j.placenta.2014.06.373] [PMID: 25064071]
Salafia CM, Yampolsky M, Misra DP, et al. Placental surface shape, function, and effects of maternal and fetal vascular pathology. Placenta 2010; 31(11): 958-62.
[http://dx.doi.org/10.1016/j.placenta.2010.09.005] [PMID: 20933281]
Loardi C, Falchetti M, Prefumo F, Facchetti F, Frusca T. Placental morphology in pregnancies associated with pregravid obesity. J Matern Fetal Neonatal Med 2016; 29(16): 2611-6.
[PMID: 26595316]
Daskalakis G, Marinopoulos S, Krielesi V, et al. Placental pathology in women with gestational diabetes. Acta Obstet Gynecol Scand 2008; 87(4): 403-7.
[http://dx.doi.org/10.1080/00016340801908783] [PMID: 18382864]
Romero R, Nien JK, Espinoza J, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med 2008; 21(1): 9-23.
[http://dx.doi.org/10.1080/14767050701830480] [PMID: 18175241]
Salvolini E, Vignini A, Sabbatinelli J, et al. Nitric oxide synthase and VEGF expression in full-term placentas of obese women. Histochem Cell Biol 2019; 152(6): 415-22.
[http://dx.doi.org/10.1007/s00418-019-01819-y] [PMID: 31552486]
Zera CA, Seely EW, Wilkins-Haug LE, Lim KH, Parry SI, McElrath TF. The association of body mass index with serum angiogenic markers in normal and abnormal pregnancies Am J Obstet Gynecol 2014; 211(3): 247- e1-7.
Eleftheriades M, Papastefanou I, Lambrinoudaki I, et al. Elevated placental growth factor concentrations at 11-14 weeks of gestation to predict gestational diabetes mellitus. Metabolism 2014; 63(11): 1419-25.
[http://dx.doi.org/10.1016/j.metabol.2014.07.016] [PMID: 25173717]
Meng Q, Shao L, Luo X, et al. Expressions of VEGF-A and VEGFR-2 in placentae from GDM pregnancies. Reprod Biol Endocrinol 2016; 14(1): 61.
[http://dx.doi.org/10.1186/s12958-016-0191-8] [PMID: 27645229]
Lappas M. Markers of endothelial cell dysfunction are increased in human omental adipose tissue from women with pre-existing maternal obesity and gestational diabetes. Metabolism 2014; 63(6): 860-73.
[http://dx.doi.org/10.1016/j.metabol.2014.03.007] [PMID: 24684825]
Murphy VE, Smith R, Giles WB, Clifton VL. Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus. Endocr Rev 2006; 27(2): 141-69.
[http://dx.doi.org/10.1210/er.2005-0011] [PMID: 16434511]
Eskild A, Fedorcsak P, Mørkrid L, Tanbo TG. Maternal body mass index and serum concentrations of human chorionic gonadotropin in very early pregnancy. Fertil Steril 2012; 98(4): 905-10.
[http://dx.doi.org/10.1016/j.fertnstert.2012.06.011] [PMID: 22769733]
Hill DJ. Placental control of metabolic adaptations in the mother for an optimal pregnancy outcome. What goes wrong in gestational di-abetes? Placenta 2018; 69: 162-8.
[http://dx.doi.org/10.1016/j.placenta.2018.01.002] [PMID: 29352600]
Newbern D, Freemark M. Placental hormones and the control of maternal metabolism and fetal growth. Curr Opin Endocrinol Diabetes Obes 2011; 18(6): 409-16.
[http://dx.doi.org/10.1097/MED.0b013e32834c800d] [PMID: 21986512]
Männik J, Vaas P, Rull K, Teesalu P, Rebane T, Laan M. Differential expression profile of growth hormone/chorionic somatomam-motropin genes in placenta of small- and large-for-gestational-age newborns. J Clin Endocrinol Metab 2010; 95(5): 2433-42.
[http://dx.doi.org/10.1210/jc.2010-0023] [PMID: 20233782]
Vakili H, Jin Y, Menticoglou S, Cattini PA. CCAAT-enhancer-binding protein β (C/EBPβ) and downstream human placental growth hormone genes are targets for dysregulation in pregnancies complicated by maternal obesity. J Biol Chem 2013; 288(31): 22849-61.
[http://dx.doi.org/10.1074/jbc.M113.474999] [PMID: 23782703]
Alsat E, Guibourdenche J, Couturier A, Evain-Brion D. Physiological role of human placental growth hormone. Mol Cell Endocrinol 1998; 140(1-2): 121-7.
[http://dx.doi.org/10.1016/S0303-7207(98)00040-9] [PMID: 9722179]
Tessier DR, Ferraro ZM, Gruslin A. Role of leptin in pregnancy: consequences of maternal obesity. Placenta 2013; 34(3): 205-11.
[http://dx.doi.org/10.1016/j.placenta.2012.11.035] [PMID: 23332215]
Walsh JM, Byrne J, Mahony RM, Foley ME, McAuliffe FM. Leptin, fetal growth and insulin resistance in non-diabetic pregnancies. Early Hum Dev 2014; 90(6): 271-4.
[http://dx.doi.org/10.1016/j.earlhumdev.2014.03.007] [PMID: 24703297]
Bao W, Baecker A, Song Y, Kiely M, Liu S, Zhang C. Adipokine levels during the first or early second trimester of pregnancy and subsequent risk of gestational diabetes mellitus: A systematic review. Metabolism 2015; 64(6): 756-64.
[http://dx.doi.org/10.1016/j.metabol.2015.01.013] [PMID: 25749468]
Jansson T, Powell TL. Role of placental nutrient sensing in developmental programming. Clin Obstet Gynecol 2013; 56(3): 591-601.
[http://dx.doi.org/10.1097/GRF.0b013e3182993a2e] [PMID: 23703224]
Segura MT, Demmelmair H, Krauss-Etschmann S, et al. Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition. Placenta 2017; 57: 144-51.
[http://dx.doi.org/10.1016/j.placenta.2017.07.001] [PMID: 28864004]
Acosta O, Ramirez VI, Lager S, et al. Increased glucose and placental glut-1 in large infants of obese nondiabetic mothers. Am J Obstet Gynecol 2015; 212(2): 227.
Gaither K, Quraishi AN, Illsley NP. Diabetes alters the expression and activity of the human placental GLUT1 glucose transporter. J Clin Endocrinol Metab 1999; 84(2): 695-701.
[http://dx.doi.org/10.1210/jc.84.2.695] [PMID: 10022440]
Song L, Sun B, Boersma GJ, et al. Prenatal high-fat diet alters placental morphology, nutrient transporter expression, and mtorc1 signaling in rat. Obesity (Silver Spring) 2017; 25(5): 909-19.
[http://dx.doi.org/10.1002/oby.21821] [PMID: 28332771]
Stanirowski PJ, Szukiewicz D, Pyzlak M, Abdalla N, Sawicki W, Cendrowski K. Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta. Endocrine 2017; 55(3): 799-808.
[http://dx.doi.org/10.1007/s12020-016-1202-4] [PMID: 27981520]
Colomiere M, Permezel M, Riley C, Desoye G, Lappas M. Defective insulin signaling in placenta from pregnancies complicated by gestational diabetes mellitus. Eur J Endocrinol 2009; 160(4): 567-78.
[http://dx.doi.org/10.1530/EJE-09-0031] [PMID: 19179458]
Jansson N, Rosario FJ, Gaccioli F, et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab 2013; 98(1): 105-13.
[http://dx.doi.org/10.1210/jc.2012-2667] [PMID: 23150676]
Jansson T, Ekstrand Y, Björn C, Wennergren M, Powell TL. Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes 2002; 51(7): 2214-9.
[http://dx.doi.org/10.2337/diabetes.51.7.2214] [PMID: 12086952]
Gaccioli F, Aye IL, Roos S, et al. Expression and functional characterisation of System L amino acid transporters in the human term placenta. Reprod Biol Endocrinol 2015; 13: 57.
[http://dx.doi.org/10.1186/s12958-015-0054-8] [PMID: 26050671]
Nandakumaran M, Al-Shammari M, Al-Saleh E. Maternal-fetal transport kinetics of L-Leucine in vitro in gestational diabetic pregnancies. Diabetes Metab 2004; 30(4): 367-74.
[http://dx.doi.org/10.1016/S1262-3636(07)70130-1] [PMID: 15525881]
Desforges M, Ditchfield A, Hirst CR, et al. Reduced placental taurine transporter (TauT) activity in pregnancies complicated by pre-eclampsia and maternal obesity. Adv Exp Med Biol 2013; 776: 81-91.
[http://dx.doi.org/10.1007/978-1-4614-6093-0_9] [PMID: 23392873]
Carter MF, Powell TL, Li C, et al. Fetal serum folate concentrations and placental folate transport in obese women. Am J Obstet Gynecol 2011; 205(1): 83.
Araújo JR, Correia-Branco A, Moreira L, Ramalho C, Martel F, Keating E. Folic acid uptake by the human syncytiotrophoblast is affected by gestational diabetes, hyperleptinemia, and TNF-α. Pediatr Res 2013; 73(4 Pt 1): 388-94.
[http://dx.doi.org/10.1038/pr.2013.14] [PMID: 23338599]
Mata-Greenwood E, Huber HF, Li C, Nathanielsz PW. Role of pregnancy and obesity on vitamin D status, transport, and metabolism in baboons. Am J Physiol Endocrinol Metab 2019; 316(1): E63-72.
[http://dx.doi.org/10.1152/ajpendo.00208.2018] [PMID: 30398904]
Knabl J, Hüttenbrenner R, Hutter S, et al. Gestational diabetes mellitus upregulates vitamin D receptor in extravillous trophoblasts and fetoplacental endothelial cells. Reprod Sci 2015; 22(3): 358-66.
[http://dx.doi.org/10.1177/1933719114542020] [PMID: 25028176]
Cho GJ, Hong SC, Oh MJ, Kim HJ. Vitamin d deficiency in gestational diabetes mellitus and the role of the placenta. Am J Obstet Gynecol 2013; 209(6): 560.
Kozłowska-Rup D, Czekaj P, Plewka D, Sikora J. Immunolocalization of ABC drug transporters in human placenta from normal and gestational diabetic pregnancies. Ginekol Pol 2014; 85(6): 410-9.
[http://dx.doi.org/10.17772/gp/1745] [PMID: 25029804]
Anger GJ, Cressman AM, Piquette-Miller M. Expression of ABC Efflux transporters in placenta from women with insulin-managed diabetes. PLoS One 2012; 7(4)e35027
[http://dx.doi.org/10.1371/journal.pone.0035027] [PMID: 22558111]
Wang C, Li H, Luo C, et al. The effect of maternal obesity on the expression and functionality of placental P-glycoprotein: Implications in the individualized transplacental digoxin treatment for fetal heart failure. Placenta 2015; 36(10): 1138-47.
[http://dx.doi.org/10.1016/j.placenta.2015.08.007] [PMID: 26311557]
Delhaes F, Giza SA, Koreman T, et al. Altered maternal and placental lipid metabolism and fetal fat development in obesity: Current knowledge and advances in non-invasive assessment. Placenta 2018; 69: 118-24.
[http://dx.doi.org/10.1016/j.placenta.2018.05.011] [PMID: 29907450]
Visiedo F, Bugatto F, Sánchez V, Cózar-Castellano I, Bartha JL, Perdomo G. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta. Am J Physiol Endocrinol Metab 2013; 305(2): E205-12.
[http://dx.doi.org/10.1152/ajpendo.00032.2013] [PMID: 23673156]
Desoye G, Gauster M, Wadsack C. Placental transport in pregnancy pathologies. Am J Clin Nutr 2011; 94(6)(Suppl.): 1896S-902S.
[http://dx.doi.org/10.3945/ajcn.110.000851] [PMID: 21543540]
Hahn T, Hartmann M, Blaschitz A, et al. Localisation of the high affinity facilitative glucose transporter protein GLUT 1 in the placenta of human, marmoset monkey (Callithrix jacchus) and rat at different developmental stages. Cell Tissue Res 1995; 280(1): 49-57.
[http://dx.doi.org/10.1007/s004410050329] [PMID: 7750136]
James-Allan LB, Arbet J, Teal SB, Powell TL, Jansson T. Insulin stimulates GLUT4 trafficking to the syncytiotrophoblast basal plasma membrane in the human placenta. J Clin Endocrinol Metab 2019; 104(9): 4225-38.
[http://dx.doi.org/10.1210/jc.2018-02778] [PMID: 31112275]
Jansson T, Wennergren M, Illsley NP. Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J Clin Endocrinol Metab 1993; 77(6): 1554-62.
[PMID: 8263141]
Vardhana PA, Illsley NP. Transepithelial glucose transport and metabolism in BeWo choriocarcinoma cells. Placenta 2002; 23(8-9): 653-60.
[http://dx.doi.org/10.1053/plac.2002.0857] [PMID: 12361684]
Rosario FJ, Kanai Y, Powell TL, Jansson T. Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth. Obesity (Silver Spring) 2015; 23(8): 1663-70.
[http://dx.doi.org/10.1002/oby.21165] [PMID: 26193061]
Camelo JS Jr, Jorge SM, Martinez FE. Amino acid composition of parturient plasma, the intervillous space of the placenta and the umbilical vein of term newborn infants. Braz J Med Biol Res 2004; 37(5): 711-7.
[http://dx.doi.org/10.1590/S0100-879X2004000500013] [PMID: 15107934]
Verrey F. System L: heteromeric exchangers of large, neutral amino acids involved in directional transport. Pflugers Arch 2003; 445(5): 529-33.
[http://dx.doi.org/10.1007/s00424-002-0973-z] [PMID: 12634921]
Gaull G, Sturman JA, Räihä NC. Development of mammalian sulfur metabolism: absence of cystathionase in human fetal tissues. Pediatr Res 1972; 6(6): 538-47.
[http://dx.doi.org/10.1203/00006450-197206000-00002] [PMID: 4625813]
Roos S, Powell TL, Jansson T. Human placental taurine transporter in uncomplicated and IUGR pregnancies: cellular localization, protein expression, and regulation. Am J Physiol Regul Integr Comp Physiol 2004; 287(4): R886-93.
[http://dx.doi.org/10.1152/ajpregu.00232.2004] [PMID: 15166008]
Baltazi M, Katsiki N, Savopoulos C, Iliadis F, Koliakos G, Hatzitolios AI. Plasma neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (a-MSH) levels in patients with or without hypertension and/or obesity: a pilot study. Am J Cardiovasc Dis 2011; 1(1): 48-59.
[PMID: 22254185]
Gill JS, Salafia CM, Grebenkov D, Vvedensky DD. Modeling oxygen transport in human placental terminal villi. J Theor Biol 2011; 291: 33-41.
[http://dx.doi.org/10.1016/j.jtbi.2011.09.008] [PMID: 21959313]
Calderon IM, Damasceno DC, Amorin RL, Costa RA, Brasil MA, Rudge MV. Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes. Diabetes Res Clin Pract 2007; 78(1): 65-71.
[http://dx.doi.org/10.1016/j.diabres.2007.01.023] [PMID: 17360067]
Taricco E, Radaelli T, Rossi G, et al. Effects of gestational diabetes on fetal oxygen and glucose levels in vivo. BJOG 2009; 116(13): 1729-35.
[http://dx.doi.org/10.1111/j.1471-0528.2009.02341.x] [PMID: 19832834]
Scott JM, Weir DG, Molloy A, McPartlin J, Daly L, Kirke P. Folic acid metabolism and mechanisms of neural tube defects. Ciba Found Symp 1994; 181: 180-7.
[PMID: 8005024]
Martino J, Segura MT, García-Valdés L, et al. The impact of maternal pre-pregnancy body weight and gestational diabetes on markers of folate metabolism in the placenta. Nutrients 2018; 10(11)E1750
[http://dx.doi.org/10.3390/nu10111750] [PMID: 30428605]
Ganguly A, Tamblyn JA, Finn-Sell S, et al. Vitamin D, the placenta and early pregnancy: effects on trophoblast function. J Endocrinol 2018; 236(2): R93-R103.
[http://dx.doi.org/10.1530/JOE-17-0491] [PMID: 29109081]
Urrutia-Pereira M, Solé D. Vitamin D deficiency in pregnancy and its impact on the fetus, the newborn and in childhood. Rev Paul Pediatr 2015; 33(1): 104-13.
[PMID: 25662013]
Ceckova-Novotna M, Pavek P, Staud F. P-glycoprotein in the placenta: expression, localization, regulation and function. Reprod Toxicol 2006; 22(3): 400-10.
[http://dx.doi.org/10.1016/j.reprotox.2006.01.007] [PMID: 16563694]
Mishra AK, Choi J, Rabbee MF, Baek KH. In silico genome-wide analysis of the atp-binding cassette transporter gene family in soybean (glycine max l) and their expression profiling. BioMed Res Int 2019; 20198150523
[PMID: 30766888]
Aye IL, Keelan JA. Placental ABC transporters, cellular toxicity and stress in pregnancy. Chem Biol Interact 2013; 203(2): 456-66.
[http://dx.doi.org/10.1016/j.cbi.2013.03.007] [PMID: 23524238]
MacFarland A, Abramovich DR, Ewen SW, Pearson CK. Stage-specific distribution of P-glycoprotein in first-trimester and full-term human placenta. Histochem J 1994; 26(5): 417-23.
[http://dx.doi.org/10.1007/BF00160054] [PMID: 7913921]
Sugawara I, Akiyama S, Scheper RJ, Itoyama S. Lung resistance protein (LRP) expression in human normal tissues in comparison with that of MDR1 and MRP. Cancer Lett 1997; 112(1): 23-31.
[http://dx.doi.org/10.1016/S0304-3835(96)04542-9] [PMID: 9029166]
Sun M, Kingdom J, Baczyk D, Lye SJ, Matthews SG, Gibb W. Expression of the multidrug resistance P-glycoprotein, (ABCB1 glycoprotein) in the human placenta decreases with advancing gestation. Placenta 2006; 27(6-7): 602-9.
[http://dx.doi.org/10.1016/j.placenta.2005.05.007] [PMID: 16143395]
Gil S, Saura R, Forestier F, Farinotti R. P-glycoprotein expression of the human placenta during pregnancy. Placenta 2005; 26(2-3): 268-70.
[http://dx.doi.org/10.1016/j.placenta.2004.05.013] [PMID: 15708129]
Atkinson DE, Greenwood SL, Sibley CP, Glazier JD, Fairbairn LJ. Role of MDR1 and MRP1 in trophoblast cells, elucidated using ret-roviral gene transfer. Am J Physiol Cell Physiol 2003; 285(3): C584-91.
[http://dx.doi.org/10.1152/ajpcell.00418.2002] [PMID: 12724138]
Pollex EK, Hutson JR. Genetic polymorphisms in placental transporters: implications for fetal drug exposure to oral antidiabetic agents. Expert Opin Drug Metab Toxicol 2011; 7(3): 325-39.
[http://dx.doi.org/10.1517/17425255.2011.553188] [PMID: 21247371]
Mason CW, Buhimschi IA, Buhimschi CS, Dong Y, Weiner CP, Swaan PW. ATP-binding cassette transporter expression in human placenta as a function of pregnancy condition. Drug Metab Dispos 2011; 39(6): 1000-7.
[http://dx.doi.org/10.1124/dmd.111.038166] [PMID: 21430233]
Lye P, Bloise E, Dunk C, et al. Effect of oxygen on multidrug resistance in the first trimester human placenta. Placenta 2013; 34(9): 817-23.
[http://dx.doi.org/10.1016/j.placenta.2013.05.010] [PMID: 23790363]
Glossmann HH, Lutz OMD. Pharmacology of metformin - An update. Eur J Pharmacol 2019; 865172782
[http://dx.doi.org/10.1016/j.ejphar.2019.172782] [PMID: 31705902]
Gui J, Liu Q, Feng L. Metformin vs insulin in the management of gestational diabetes: a meta-analysis. PLoS One 2013; 8(5)e64585
[http://dx.doi.org/10.1371/journal.pone.0064585] [PMID: 23724063]
Guo L, Ma J, Tang J, Hu D, Zhang W, Zhao X. Comparative efficacy and safety of metformin, glyburide, and insulin in treating gestational diabetes mellitus: A meta-analysis. J Diabetes Res 2019; 20199804708
[http://dx.doi.org/10.1155/2019/9804708] [PMID: 31781670]
Feng Y, Yang H. Metformin - a potentially effective drug for gestational diabetes mellitus: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2017; 30(15): 1874-81.
[http://dx.doi.org/10.1080/14767058.2016.1228061] [PMID: 27549367]
Syngelaki A, Nicolaides KH, Balani J, et al. Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med 2016; 374(5): 434-43.
[http://dx.doi.org/10.1056/NEJMoa1509819] [PMID: 26840133]
Rowan JA, Rush EC, Obolonkin V, Battin M, Wouldes T, Hague WM. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition at 2 years of age. Diabetes Care 2011; 34(10): 2279-84.
[http://dx.doi.org/10.2337/dc11-0660] [PMID: 21949222]
Rowan JA, Rush EC, Plank LD, et al. Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age. BMJ Open Diabetes Res Care 2018; 6(1)e000456
[http://dx.doi.org/10.1136/bmjdrc-2017-000456] [PMID: 29682291]
Wouldes TA, Battin M, Coat S, Rush EC, Hague WM, Rowan JA. Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes. Arch Dis Child Fetal Neonatal Ed 2016; 101(6): F488-93.
[http://dx.doi.org/10.1136/archdischild-2015-309602] [PMID: 26912348]
Chiswick C, Reynolds RM, Denison F, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2015; 3(10): 778-86.
[http://dx.doi.org/10.1016/S2213-8587(15)00219-3] [PMID: 26165398]
Rø TB, Ludvigsen HV, Carlsen SM, Vanky E. Growth, body composition and metabolic profile of 8-year-old children exposed to metformin in utero. Scand J Clin Lab Invest 2012; 72(7): 570-5.
[http://dx.doi.org/10.3109/00365513.2012.712319] [PMID: 22935043]
Brownfoot FC, Hastie R, Hannan NJ, et al. Metformin as a prevention and treatment for preeclampsia: Effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction. Am J Obstet Gynecol 2016; 214(3): 356.
Alqudah A, McKinley MC, McNally R, et al. Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis. Diabet Med 2018; 35(2): 160-72.
[http://dx.doi.org/10.1111/dme.13523] [PMID: 29044702]
Huhtala MS, Tertti K, Pellonperä O, Rönnemaa T. Amino acid profile in women with gestational diabetes mellitus treated with metformin or insulin. Diabetes Res Clin Pract 2018; 146: 8-17.
[http://dx.doi.org/10.1016/j.diabres.2018.09.014] [PMID: 30227169]
Borengasser SJ, Baker PR II, Kerns ME, et al. Preconception micronutrient supplementation reduced circulating branched chain amino acids at 12 weeks gestation in an open trial of guatemalan women who are overweight or obese. Nutrients 2018; 10(9)E1282
[http://dx.doi.org/10.3390/nu10091282] [PMID: 30208589]
Ji Y, Wu Z, Dai Z, Sun K, Wang J, Wu G. Nutritional epigenetics with a focus on amino acids: implications for the development and treatment of metabolic syndrome. J Nutr Biochem 2016; 27: 1-8.
[http://dx.doi.org/10.1016/j.jnutbio.2015.08.003] [PMID: 26427799]
Tipi-Akbas P, Arioz DT, Kanat-Pektas M, Koken T, Koken G, Yilmazer M. Lowered serum total L-carnitine levels are associated with obesity at term pregnancy. J Matern Fetal Neonatal Med 2013; 26(15): 1479-83.
[http://dx.doi.org/10.3109/14767058.2013.789847] [PMID: 23560471]
Scioscia M, Karumanchi SA, Goldman-Wohl D, Robillard PY. Endothelial dysfunction and metabolic syndrome in preeclampsia: an alternative viewpoint. J Reprod Immunol 2015; 108: 42-7.
[http://dx.doi.org/10.1016/j.jri.2015.01.009] [PMID: 25766966]
Sobota-Grzeszyk A, Kuźmicki M, Szamatowicz J. Myoinositol in the prevention of gestational diabetes mellitus: Is it sensible? J Diabetes Res 2019; 20193915253
[http://dx.doi.org/10.1155/2019/3915253] [PMID: 31886278]
Stuart TJ, O’Neill K, Condon D, et al. Diet-induced obesity alters the maternal metabolome and early placenta transcriptome and decreases placenta vascularity in the mouse. Biol Reprod 2018; 98(6): 795-809.
[http://dx.doi.org/10.1093/biolre/ioy010] [PMID: 29360948]
Corrado F, D’Anna R, Di Vieste G, et al. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med 2011; 28(8): 972-5.
[http://dx.doi.org/10.1111/j.1464-5491.2011.03284.x] [PMID: 21414183]
D’Anna R, Scilipoti A, Giordano D, et al. myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. Diabetes Care 2013; 36(4): 854-7.
[http://dx.doi.org/10.2337/dc12-1371] [PMID: 23340885]
DʼAnna R, , Di Benedetto A, Scilipoti A, et al. Myo-inositol supplementation for prevention of gestational diabetes in obese pregnant women: A randomized controlled trial. Obstet Gynecol 2015; 126(2): 310-5.
[http://dx.doi.org/10.1097/AOG.0000000000000958] [PMID: 26241420]
Santamaria A, Di Benedetto A, Petrella E, et al. Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. J Matern Fetal Neonatal Med 2016; 29(19): 3234-7.
[http://dx.doi.org/10.3109/14767058.2015.1121478] [PMID: 26698911]
Crawford TJ, Crowther CA, Alsweiler J, Brown J. Antenatal dietary supplementation with myo-inositol in women during pregnancy for preventing gestational diabetes. Cochrane Database Syst Rev 2015; 12CD011507
[http://dx.doi.org/10.1002/14651858.CD011507.pub2] [PMID: 26678256]
Nanobashvili K, Jack-Roberts C, Bretter R, et al. Maternal choline and betaine supplementation modifies the placental response to hy-perglycemia in mice and human trophoblasts. Nutrients 2018; 10(10)E1507
[http://dx.doi.org/10.3390/nu10101507] [PMID: 30326592]
Sivanesan S, Taylor A, Zhang J, Bakovic M. Betaine and choline improve lipid homeostasis in obesity by participation in mitochondrial oxidative demethylation. Front Nutr 2018; 5: 61.
[http://dx.doi.org/10.3389/fnut.2018.00061] [PMID: 30042948]
Joselit Y, Nanobashvili K, Jack-Roberts C, et al. Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner. Nutr Diabetes 2018; 8(1): 41.
[http://dx.doi.org/10.1038/s41387-018-0035-z] [PMID: 30026535]
Jack-Roberts C, Joselit Y, Nanobashvili K, et al. Choline supplementation normalizes fetal adiposity and reduces lipogenic gene expression in a mouse model of maternal obesity. Nutrients 2017; 9(8)E899
[http://dx.doi.org/10.3390/nu9080899] [PMID: 28820499]
Nam J, Greenwald E, Jack-Roberts C, et al. Choline prevents fetal overgrowth and normalizes placental fatty acid and glucose metabolism in a mouse model of maternal obesity. J Nutr Biochem 2017; 49: 80-8.
[http://dx.doi.org/10.1016/j.jnutbio.2017.08.004] [PMID: 28915389]
Jiang X, Bar HY, Yan J, et al. A higher maternal choline intake among third-trimester pregnant women lowers placental and circulating concentrations of the antiangiogenic factor fms-like tyrosine kinase-1 (sFLT1). FASEB J 2013; 27(3): 1245-53.
[http://dx.doi.org/10.1096/fj.12-221648] [PMID: 23195033]
Benigni A, Gregorini G, Frusca T, et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med 1989; 321(6): 357-62.
[http://dx.doi.org/10.1056/NEJM198908103210604] [PMID: 2664523]
Mirabito Colafella KM, Neuman RI, Visser W, Danser AHJ, Versmissen J. Aspirin for the prevention and treatment of pre-eclampsia: A matter of COX-1 and/or COX-2 inhibition? Basic Clin Pharmacol Toxicol 2020; 127(2): 132-41.
[http://dx.doi.org/10.1111/bcpt.13308] [PMID: 31420920]
Nelson DM, Walsh SW. Aspirin differentially affects thromboxane and prostacyclin production by trophoblast and villous core compartments of human placental villi. Am J Obstet Gynecol 1989; 161(6 Pt 1): 1593-8.
[http://dx.doi.org/10.1016/0002-9378(89)90932-0] [PMID: 2513721]
Diss EM, Gabbe SG, Moore JW, Kniss DA. Study of thromboxane and prostacyclin metabolism in an in vitro model of first-trimester human trophoblast. Am J Obstet Gynecol 1992; 167(4 Pt 1): 1046-52.
[http://dx.doi.org/10.1016/S0002-9378(12)80036-6] [PMID: 1415390]
Bowen RS, Zhang Y, Gu Y, Lewis DF, Wang Y. Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition. Placenta 2005; 26(5): 402-9.
[http://dx.doi.org/10.1016/j.placenta.2004.07.007] [PMID: 15850645]
Roberge S, Bujold E, Nicolaides KH. Aspirin for the prevention of preterm and term preeclampsia: Systematic review and metaanalysis. Am J Obstet Gynecol 2018; 218(3): 287-93.
Bujold E, Roberge S, Lacasse Y, et al. Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a meta-analysis. Obstet Gynecol 2010; 116(2 Pt 1): 402-14.
[http://dx.doi.org/10.1097/AOG.0b013e3181e9322a] [PMID: 20664402]
Duley L, Meher S, Hunter KE, Seidler AL, Askie LM. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev 2019; 10CD004659
[http://dx.doi.org/10.1002/14651858.CD004659.pub3] [PMID: 31684684]
Hypertension in pregnancy: Diagnosis and management..
Eastabrook G, Aksoy T, Bedell S, Penava D, de Vrijer B. Preeclampsia biomarkers: An assessment of maternal cardiometabolic health. Pregnancy Hypertens 2018; 13: 204-13.
[http://dx.doi.org/10.1016/j.preghy.2018.06.005] [PMID: 30177053]
Barden A, Singh R, Walters BN, Ritchie J, Roberman B, Beilin LJ. Factors predisposing to pre-eclampsia in women with gestational diabetes. J Hypertens 2004; 22(12): 2371-8.
[http://dx.doi.org/10.1097/00004872-200412000-00020] [PMID: 15614032]
Dieber-Rotheneder M, Beganovic S, Desoye G, Lang U, Cervar-Zivkovic M. Complex expression changes of the placental endothelin system in early and late onset preeclampsia, fetal growth restriction and gestational diabetes. Life Sci 2012; 91(13-14): 710-5.
[http://dx.doi.org/10.1016/j.lfs.2012.04.040] [PMID: 22580289]
Poon LC, Wright D, Rolnik DL, et al. Aspirin for evidence-based preeclampsia prevention trial: Effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history. Am J Obstet Gynecol 2017; 217(5): 585.
Brill MJ, Diepstraten J, van Rongen A, van Kralingen S, van den Anker JN, Knibbe CA. Impact of obesity on drug metabolism and elimination in adults and children. Clin Pharmacokinet 2012; 51(5): 277-304.
[http://dx.doi.org/10.2165/11599410-000000000-00000] [PMID: 22448619]
Finneran MM, Gonzalez-Brown VM, Smith DD, Landon MB, Rood KM. Obesity and laboratory aspirin resistance in high-risk pregnant women treated with low-dose aspirin. Am J Obstet Gynecol 2019; 220(4): 385.
Marseglia L, D’Angelo G, Manti S, Reiter RJ, Gitto E. Potential utility of melatonin in preeclampsia, intrauterine fetal growth retardation, and perinatal asphyxia. Reprod Sci 2016; 23(8): 970-7.
[http://dx.doi.org/10.1177/1933719115612132] [PMID: 26566856]
Milczarek R, Hallmann A, Sokołowska E, Kaletha K, Klimek J. Melatonin enhances antioxidant action of alpha-tocopherol and ascorbate against NADPH- and iron-dependent lipid peroxidation in human placental mitochondria. J Pineal Res 2010; 49(2): 149-55.
[PMID: 20524970]
Reiter RJ, Tan DX, Korkmaz A. The circadian melatonin rhythm and its modulation: possible impact on hypertension. J Hypertens Suppl 2009; 27(6): S17-20.
[http://dx.doi.org/10.1097/01.hjh.0000358832.41181.bf] [PMID: 19633446]
Prado NJ, Ferder L, Manucha W, Diez ER. Anti-inflammatory effects of melatonin in obesity and hypertension. Curr Hypertens Rep 2018; 20(5): 45.
[http://dx.doi.org/10.1007/s11906-018-0842-6] [PMID: 29744660]
Lanoix D, Beghdadi H, Lafond J, Vaillancourt C. Human placental trophoblasts synthesize melatonin and express its receptors. J Pineal Res 2008; 45(1): 50-60.
[http://dx.doi.org/10.1111/j.1600-079X.2008.00555.x] [PMID: 18312298]
Hobson SR, Gurusinghe S, Lim R, et al. Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia. J Pineal Res 2018; 65(3)e12508
[http://dx.doi.org/10.1111/jpi.12508] [PMID: 29766570]
Nakamura Y, Tamura H, Kashida S, et al. Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy. J Pineal Res 2001; 30(1): 29-33.
[http://dx.doi.org/10.1034/j.1600-079X.2001.300104.x] [PMID: 11168904]
Tranquilli AL, Turi A, Giannubilo SR, Garbati E. Circadian melatonin concentration rhythm is lost in pregnant women with altered blood pressure rhythm. Gynecol Endocrinol 2004; 18(3): 124-9.
[http://dx.doi.org/10.1080/09513590410001667841] [PMID: 15255280]
Murthi P, Vaillancourt C. Placental serotonin systems in pregnancy metabolic complications associated with maternal obesity and ges-tational diabetes mellitus. Biochim Biophys Acta Mol Basis Dis 2020; 1866(2)165391
[http://dx.doi.org/10.1016/j.bbadis.2019.01.017] [PMID: 30738809]
Galano A, Castañeda-Arriaga R, Pérez-González A, Tan DX, Reiter RJ. Phenolic melatonin-related compounds: Their role as chemical protectors against oxidative stress. Molecules 2016; 21(11)E1442
[http://dx.doi.org/10.3390/molecules21111442] [PMID: 27801875]
Leitner M, Fragner L, Danner S, et al. Combined metabolomic analysis of plasma and urine reveals ahba, tryptophan and serotonin metabolism as potential risk factors in gestational diabetes mellitus (gdm). Front Mol Biosci 2017; 4: 84.
[http://dx.doi.org/10.3389/fmolb.2017.00084] [PMID: 29312952]
Almaça J, Molina J, Menegaz D, et al. Human beta cells produce and release serotonin to inhibit glucagon secretion from alpha cells. Cell Rep 2016; 17(12): 3281-91.
[http://dx.doi.org/10.1016/j.celrep.2016.11.072] [PMID: 28009296]
Middelkoop CM, Dekker GA, Kraayenbrink AA, Popp-Snijders C. Platelet-poor plasma serotonin in normal and preeclamptic pregnancy. Clin Chem 1993; 39(8): 1675-8.
[http://dx.doi.org/10.1093/clinchem/39.8.1675] [PMID: 8353954]
Blazevic S, Horvaticek M, Kesic M, et al. Epigenetic adaptation of the placental serotonin transporter gene (SLC6A4) to gestational di-abetes mellitus. PLoS One 2017; 12(6)e0179934
[http://dx.doi.org/10.1371/journal.pone.0179934] [PMID: 28650965]
Viau M, Lafond J, Vaillancourt C. Expression of placental serotonin transporter and 5-HT 2A receptor in normal and gestational diabetes mellitus pregnancies. Reprod Biomed Online 2009; 19(2): 207-15.
[http://dx.doi.org/10.1016/S1472-6483(10)60074-0] [PMID: 19712556]
Sen S, Iyer C, Meydani SN. Obesity during pregnancy alters maternal oxidant balance and micronutrient status. J Perinatol 2014; 34(2): 105-11.
[http://dx.doi.org/10.1038/jp.2013.153] [PMID: 24355940]
Sen S, Simmons RA. Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats. Diabetes 2010; 59(12): 3058-65.
[http://dx.doi.org/10.2337/db10-0301] [PMID: 20823102]
Maged AM, Torky H, Fouad MA, et al. Role of antioxidants in gestational diabetes mellitus and relation to fetal outcome: a randomized controlled trial. J Matern Fetal Neonatal Med 2016; 29(24): 4049-54.
[http://dx.doi.org/10.3109/14767058.2016.1154526] [PMID: 26999688]
Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev 2015; 9CD004072
[PMID: 26415762]
Rumbold A, Ota E, Hori H, Miyazaki C, Crowther CA. Vitamin E supplementation in pregnancy. Cochrane Database Syst Rev 2015; 9CD004069
[PMID: 26343254]
Son JS, Liu X, Tian Q, et al. Exercise prevents the adverse effects of maternal obesity on placental vascularization and fetal growth. J Physiol 2019; 597(13): 3333-47.
[http://dx.doi.org/10.1113/JP277698] [PMID: 31115053]
Davies GAL, Wolfe LA, Mottola MF, MacKinnon C. No. 129-exercise in pregnancy and the postpartum period. J Obstet Gynaecol Can 2018; 40(2): e58-65.
[http://dx.doi.org/10.1016/j.jogc.2017.11.001] [PMID: 29447726]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 16 June, 2020
Page: [176 - 192]
Pages: 17
DOI: 10.2174/1570161118666200616144512
Price: $65

Article Metrics

PDF: 42