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Expression of cholesterol packaging and transport genes in human and rat placenta: impact of obesity and a high-fat diet

Published online by Cambridge University Press:  11 October 2019

Sally A. V. Draycott*
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK Food and Nutrition Research Group, Department of Food and Wine Science, School of Agriculture Food and Wine, University of Adelaide, Adelaide, Australia
Zoe Daniel
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK
Raheela Khan
Affiliation:
Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, The Royal Derby Hospital, University of Nottingham, Derby, UK
Beverly S. Muhlhausler
Affiliation:
Food and Nutrition Research Group, Department of Food and Wine Science, School of Agriculture Food and Wine, University of Adelaide, Adelaide, Australia Commonwealth Scientific and Industrial Research Organisation, Adelaide, Australia
Matthew J. Elmes
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK
Simon C. Langley-Evans
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK
*
Address for correspondence: Sally A. V. Draycott, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, UK, Email: sally.draycott@nottingham.ac.uk

Abstract

Evidence suggests that sub-optimal maternal nutrition has implications for the developing offspring. We have previously shown that exposure to a low-protein diet during gestation was associated with upregulation of genes associated with cholesterol transport and packaging within the placenta. This study aimed to elucidate the effect of altering maternal dietary linoleic acid (LA; omega-6) to alpha-linolenic acid (ALA; omega-6) ratios as well as total fat content on placental expression of genes associated with cholesterol transport. The potential for maternal body mass index (BMI) to be associated with expression of these genes in human placental samples was also evaluated. Placentas were collected from 24 Wistar rats at 20-day gestation (term = 21–22-day gestation) that had been fed one of four diets containing varying fatty acid compositions during pregnancy, and from 62 women at the time of delivery. Expression of 14 placental genes associated with cholesterol packaging and transfer was assessed in rodent and human samples by quantitative real time polymerase chain reaction. In rats, placental mRNA expression of ApoA2, ApoC2, Cubn, Fgg, Mttp and Ttr was significantly elevated (3–30 fold) in animals fed a high LA (36% fat) diet, suggesting increased cholesterol transport across the placenta in this group. In women, maternal BMI was associated with fewer inconsistent alterations in gene expression. In summary, sub-optimal maternal nutrition is associated with alterations in the expression of genes associated with cholesterol transport in a rat model. This may contribute to altered fetal development and potentially programme disease risk in later life. Further investigation of human placenta in response to specific dietary interventions is required.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

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References

Langley-Evans, SC.Nutrition in early life and the programming of adult disease: a review. J Hum Nutr Diet. 2015; 28, Suppl 1, 114.CrossRefGoogle ScholarPubMed
Le Clair, C, Abbi, T, Sandhu, H, Tappia, PS.Impact of maternal undernutrition on diabetes and cardiovascular disease risk in adult offspring. Can J Physiol Pharmacol. 2009; 87(3), 161179.CrossRefGoogle ScholarPubMed
Langley-Evans, SC.Fetal programming of CVD and renal disease: animal models and mechanistic considerations. Proc Nutr Soc. 2013; 72(3), 317325.CrossRefGoogle ScholarPubMed
Godfrey, KM, Reynolds, RM, Prescott, SL, et al.Influence of maternal obesity on the long-term health of offspring. Lancet Diabetes Endocrinol. 2017; 5(1), 5364.CrossRefGoogle ScholarPubMed
Ribaroff, GA, Wastnedge, E, Drake, AJ, Sharpe, RM, Chambers, TJG.Animal models of maternal high fat diet exposure and effects on metabolism in offspring: a meta-regression analysis. Obes Rev. 2017; 18(6), 673686.CrossRefGoogle ScholarPubMed
Ainge, H, Thompson, C, Ozanne, SE, Rooney, KB.A systematic review on animal models of maternal high fat feeding and offspring glycaemic control. Int J Obes (Lond). 2011; 35(3), 325335.CrossRefGoogle ScholarPubMed
Muhlhausler, BS, Ailhaud, GP.Omega-6 polyunsaturated fatty acids and the early origins of obesity. Curr Opin Endocrinol Diabetes Obes. 2013; 20(1), 5661.CrossRefGoogle ScholarPubMed
Ramsden, CE, Faurot, KR, Zamora, D, et al.Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. Pain. 2013; 154(11), 24412451.CrossRefGoogle ScholarPubMed
Blasbalg, TL, Hibbeln, JR, Ramsden, CE, Majchrzak, SF, Rawlings, RR.Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011; 93(5), 950962.CrossRefGoogle ScholarPubMed
Sioen, I, van Lieshout, L, Eilander, A, et al.Systematic review on N-3 and N-6 polyunsaturated fatty acid intake in European countries in light of the current recommendations – focus on specific population groups. Ann Nutr Metab. 2017; 70(1), 3950.CrossRefGoogle ScholarPubMed
Tarrade, A, Panchenko, P, Junien, C, Gabory, A.Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism. J Exp Biol. 2015; 218(Pt 1), 5058.CrossRefGoogle ScholarPubMed
Singh, P, Saxena, R, Srinivas, G, Pande, G, Chattopadhyay, A.Cholesterol biosynthesis and homeostasis in regulation of the cell cycle. PLoS One, 2013; 8(3), e58833.CrossRefGoogle ScholarPubMed
Fernández, C, Martín, M, Gómez-Coronado, D, Lasunción, MA.Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression. J Lipid Res. 2005; 46(5), 920929.CrossRefGoogle ScholarPubMed
Porter, FD.Malformation syndromes due to inborn errors of cholesterol synthesis. J Clin Invest. 2002; 110(6), 715724.CrossRefGoogle ScholarPubMed
Maymunah, AO, Kehinde, O, Abidoye, G, Oluwatosin, A.Hypercholesterolaemia in pregnancy as a predictor of adverse pregnancy outcome. Afr Health Sci. 2014; 14(4), 967973.CrossRefGoogle ScholarPubMed
Edison, RJ, Berg, K, Remaley, A, et al.Adverse birth outcome among mothers with low serum cholesterol. Pediatrics. 2007; 120(4), 723733.CrossRefGoogle ScholarPubMed
Baardman, ME, Kerstjens-Frederikse, WS, Berger, RM, et al.The role of maternal-fetal cholesterol transport in early fetal life: current insights. Biol Reprod. 2013; 88(1), 24.CrossRefGoogle ScholarPubMed
Woollett, LA.Review: transport of maternal cholesterol to the fetal circulation. Placenta. 2011; 32, Suppl 2, S218S221.CrossRefGoogle ScholarPubMed
Stefulj, J, Panzenboeck, U, Becker, T, et al.Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circ Res. 2009; 104(5), 600608.CrossRefGoogle ScholarPubMed
Madsen, EM, Lindegaard, ML, Andersen, CB, Damm, P, Nielsen, LB, Human placenta secretes apolipoprotein B-100-containing lipoproteins. J Biol Chem. 2004; 279(53), 5527155276.CrossRefGoogle ScholarPubMed
Daniel, Z, Swali, A, Emes, R, Langley-Evans, SC.The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport. Genes Nutr. 2016; 11(1), 27.CrossRefGoogle ScholarPubMed
Langley, SC, Jackson, AA.Increased systolic blood pressure in adult rats induced by fetal exposure to maternal low protein diets. Clin Sci (Lond). 1994; 86(2), 217222; discussion 121.CrossRefGoogle ScholarPubMed
Erhuma, A, Salter, AM, Sculley, DV, Langley-Evans, SC, Bennett, AJ.Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat. Am J Physiol Endocrinol Metab. 2007; 292(6), E1702E1714.CrossRefGoogle ScholarPubMed
Swali, A, McMullen, S, Hayes, H, et al.Cell Cycle regulation and cytoskeletal remodelling are critical processes in the nutritional programming of embryonic development. PLoS One. 2011; 6(8), e23189.CrossRefGoogle ScholarPubMed
McMullen, S, Langley-Evans, SC, Gambling, L, et al.A common cause for a common phenotype: the gatekeeper hypothesis in fetal programming. Med Hypotheses. 2012; 78(1), 8894.CrossRefGoogle ScholarPubMed
Draycott, SAV, Liu, G, Daniel, ZC, et al.Maternal dietary ratio of linoleic acid to alpha-linolenic acid during pregnancy has sex-specific effects on placental and fetal weights in the rat. Nutr Metab. 2019; 16(1), 1.CrossRefGoogle ScholarPubMed
McClive, PJ, Sinclair, AH.Rapid DNA extraction and PCR-sexing of mouse embryos. Mol Reprod Dev. 2001; 60(2), 225226.CrossRefGoogle ScholarPubMed
Bhasin, KK, van Nas, A, Martin, LJ, et al.Maternal low-protein diet or hypercholesterolemia reduces circulating essential amino acids and leads to intrauterine growth restriction. Diabetes. 2009; 58(3), 559566.CrossRefGoogle ScholarPubMed
El-Sayyad, HI, Al-Haggar, MM, El-Ghawet, HA, Bakr, IH.Effect of maternal diabetes and hypercholesterolemia on fetal liver of albino Wistar rats. Nutrition. 2014; 30(3), 326336.CrossRefGoogle ScholarPubMed
Napoli, C, de Nigris, F, Welch, JS, et al.Maternal hypercholesterolemia during pregnancy promotes early atherogenesis in LDL receptor-deficient mice and alters aortic gene expression determined by microarray. Circulation. 2002; 105(11), 13601367.CrossRefGoogle ScholarPubMed
Goharkhay, N, Sbrana, E, Gamble, PK, et al.Characterization of a murine model of fetal programming of atherosclerosis. Am J Obstet Gynecol. 2007; 197(4), 416.e1416.e5.CrossRefGoogle ScholarPubMed
Papacleovoulou, G, Abu-Hayyeh, S, Nikolopoulou, E, et al.Maternal cholestasis during pregnancy programs metabolic disease in offspring. J Clin Invest. 2013; 123(7), 31723181.CrossRefGoogle ScholarPubMed
Napoli, C, D’Armiento, FP, Mancini, FP, et al.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. 1997; 100(11), 26802690.CrossRefGoogle ScholarPubMed
Solini, A, Santini, E, Madec, S, Rossi, C, Muscelli, E, Retinol-binding protein-4 in women with untreated essential hypertension. Am J Hypertens. 2009; 22(9), 10011006.CrossRefGoogle ScholarPubMed
Yang, Q, Graham, TE, Mody, N, et al.Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005; 436(7049), 356362.CrossRefGoogle ScholarPubMed
Graham, TE, Yang, Q, Blüher, M, et al.Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med, 2006; 354(24), 25522563.CrossRefGoogle ScholarPubMed
Dubé, E, Gravel, A, Martin, C, et al.Modulation of fatty acid transport and metabolism by maternal obesity in the human full-term placenta. Biol Reprod. 2012; 87(1), 14, 1–11.CrossRefGoogle ScholarPubMed
Barkley, MS, Geschwind, II, Bradford, GE, The gestational pattern of estradiol, testosterone and progesterone secretion in selected strains of mice. Biol Reprod. 1979; 20(4), 733738.CrossRefGoogle ScholarPubMed
Tal, R, Taylor, HS, Burney, RO, Mooney, SB, Giudice, LC.Endocrinology of pregnancy. In Endotext (eds. Feingold, KRet al.), 2000; MDText.com, Inc., South Dartmouth (MA).Google ScholarPubMed
Mullen, MP, Forde, N, Parr, MH, et al.Alterations in systemic concentrations of progesterone during the early luteal phase affect RBP4 expression in the bovine uterus. Reprod Fertil Dev. 2012; 24(5), 715722.CrossRefGoogle ScholarPubMed
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