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A maternal high-fat diet in rat pregnancy reduces growth of the fetus and the placental junctional zone, but not placental labyrinth zone growth

  • P. J. Mark (a1), C. Sisala (a1), K. Connor (a2), R. Patel (a2), J. L. Lewis (a1), M. H. Vickers (a2), B. J. Waddell (a1) and D. M. Sloboda (a2)...

Abstract

Maternal obesity during pregnancy is often characterized by fetal macrosomia but it can also result in fetal growth restriction in a subset of pregnancies. We hypothesized that mechanisms of this growth restriction may include adverse effects of maternal high fat (HF) intake on placental growth and function. Female rats (100 days old) were time-mated and randomly assigned to either a control (Con) or HF diet ad libitum throughout gestation. At E21, dams were killed; litter size and fetal and placental weights were recorded and maternal and fetal samples collected for further analyses. The HF diet resulted in a 54% increase in maternal body weight gain during gestation. In contrast, male and female fetal weights were reduced in HF pregnancies (P < 0.05), as were the weights of the junctional zone of the placenta (P = 0.013), whereas labyrinth zone weights were unaffected. The HF diet increased maternal and fetal plasma leptin levels (P < 0.05), but maternal and fetal insulin and fetal glucose levels were unaffected. Labyrinthine expression of PPARγ and total VEGFa mRNA, both markers of placental vascular development, were unaffected by consumption of the HF diet in placentas of male and female fetuses. Furthermore, maternal HF nutrition did not alter phosphorylated protein levels of either mammalian target of rapamycin or its downstream signaling factor eIF4E binding protein 1 (4E-BP1). These data show that in the rat, maternal HF nutrition results in fetal and placental junctional zone growth restriction, maternal and fetal hyperleptinemia but did not alter gene expression of markers of placental vascular development.

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Corresponding author

*Address for correspondence: P. J. Mark, PhD, School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia. (Email peter.mark@uwa.edu.au)

References

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1.Schrauwers, C, Dekker, G. Maternal and perinatal outcome in obese pregnant patients. J Matern Fetal Neonatal Med. 2009; 22, 218226.
2.Ogden, CL, Carroll, MD, Curtin, LR, et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006; 295, 15491555.
3.Kristensen, J, Vestergaard, M, Wisborg, K, Kesmodel, U, Secher, NJ. Pre-pregnancy weight and the risk of stillbirth and neonatal death. BJOG. 2005; 112, 403408.
4.Ehrenberg, HM, Mercer, BM, Catalano, PM. The influence of obesity and diabetes on the prevalence of macrosomia. Am J Obstet Gynecol. 2004; 191, 964968.
5.Jaipaul, JV, Newburn-Cook, CV, O'Brien, B, Demianczuk, N. Modifiable risk factors for term large for gestational age births. Health Care Women Int. 2009; 30, 802823.
6.Perlow, JH, Morgan, MA, Montgomery, D, Towers, CV, Porto, M. Perinatal outcome in pregnancy complicated by massive obesity. Am J Obstet Gynecol. 1992; 167, 958962.
7.Mathew, M, Machado, L, Al-Ghabshi, R, Al-Haddabi, R. Fetal macrosomia. Risk factor and outcome. Saudi Med J. 2005; 26, 96100.
8.Gardosi, J, Francis, A. Adverse pregnancy outcome and association with small for gestational age birthweight by customized and population-based percentiles. Am J Obstet Gynecol. 2009; 201, 28e128e8.
9.Akyol, A, Langley-Evans, SC, McMullen, S. Obesity induced by cafeteria feeding and pregnancy outcome in the rat. Br J Nutr. 2009; 102, 16011610.
10.Howie, GJ, Sloboda, DM, Kamal, T, Vickers, MH. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. 2009; 587, 905915.
11.Barker, DJ. Fetal growth and adult disease. Br J Obstet Gynaecol. 1992; 99, 275276.
12.Barker, DJ, Osmond, C, Golding, J, Kuh, D, Wadsworth, ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989; 298, 564567.
13.de Rooij, SR, Painter, RC, Phillips, DI, et al. Impaired insulin secretion after prenatal exposure to the Dutch famine. Diabetes Care. 2006; 29, 18971901.
14.de Rooij, SR, Painter, RC, Roseboom, TJ, et al. Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine. Diabetologia. 2006; 49, 637643.
15.Gagnon, R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003; 110(Suppl. 1), S99S107.
16.Jansson, T, Powell, TL. Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clin Sci (Lond). 2007; 113, 113.
17.Seckl, JR, Benediktsson, R, Lindsay, RS, Brown, RW. Placental 11 beta-hydroxysteroid dehydrogenase and the programming of hypertension. J Steroid Biochem Mol Biol. 1995; 55, 447455.
18.Wyrwoll, CS, Seckl, JR, Holmes, MC. Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice. Endocrinology. 2009; 150, 12871293.
19.Hewitt, DP, Mark, PJ, Waddell, BJ. Glucocorticoids prevent the normal increase in placental vascular endothelial growth factor expression and placental vascularity during late pregnancy in the rat. Endocrinology. 2006; 147, 55685574.
20.Wyrwoll, CS, Mark, PJ, Mori, TA, Puddey, IB, Waddell, BJ. Prevention of programmed hyperleptinemia and hypertension by postnatal dietary omega-3 fatty acids. Endocrinology. 2006; 147, 599606.
21.Smith, JT, Waddell, BJ. Leptin distribution and metabolism in the pregnant rat: transplacental leptin passage increases in late gestation but is reduced by excess glucocorticoids. Endocrinology. 2003; 144, 30243030.
22.Le Bacquer, O, Petroulakis, E, Paglialunga, S, et al. Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2. J Clin Invest. 2007; 117, 387396.
23.Um, SH, Frigerio, F, Watanabe, M, et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature. 2004; 431, 200205.
24.Roos, S, Jansson, N, Palmberg, I, et al. Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth. J Physiol. 2007; 582, 449459.
25.Roos, S, Powell, TL, Jansson, T. Placental mTOR links maternal nutrient availability to fetal growth. Biochem Soc Trans. 2009; 37, 295298.
26.Sloboda, DM, Howie, GJ, Pleasants, A, Gluckman, PD, Vickers, MH. Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat. PLoS One. 2009; 4, e6744.
27.Barak, Y, Nelson, MC, Ong, ES, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell. 1999; 4, 585595.
28.Hewitt, DP, Mark, PJ, Waddell, BJ. Placental expression of peroxisome proliferator-activated receptors in rat pregnancy and the effect of increased glucocorticoid exposure. Biol Reprod. 2006; 74, 2328.
29.Pathipati, P, Surus, A, Williams, CE, Scheepens, A. Delayed and chronic treatment with growth hormone after endothelin-induced stroke in the adult rat. Behav Brain Res. 2009; 204, 93101.
30.Lareu, RR, Harve, KS, Raghunath, M. Emulating a crowded intracellular environment in vitro dramatically improves RT-PCR performance. Biochem Biophys Res Commun. 2007; 363, 171177.
31.Rozen, S, Skaletsky, HJ. Primer3 on the WWW for general users and for biologist programmers. In Bioinformatics Methods and Protocols: Methods in Molecular Biology (eds. Krawetz S, Misener S), 2000; pp. 365386. Humana Press: Totowa, NJ.
32.Vandesompele, J, De Preter, K, Pattyn, F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3, RESEARCH0034, 111.
33.Snedecor, G, Cochrane, W. Statistical Methods 1989. Iowa State University Press: Ames, IA.
34.Coan, PM, Vaughan, OR, Sekita, Y, et al. Adaptations in placental phenotype support fetal growth during undernutrition of pregnant mice. J Physiol. 2010; 527538.
35.Gangloff, YG, Mueller, M, Dann, SG, et al. Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development. Mol Cell Biol. 2004; 24, 95089516.
36.Mparmpakas, D, Zachariades, E, Foster, H, et al. Expression of mTOR and downstream signalling components in the JEG-3 and BeWo human placental choriocarcinoma cell lines. Int J Mol Med. 2010; 25, 6569.
37.Jansson, N, Pettersson, J, Haafiz, A, et al. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol. 2006; 576, 935946.
38.Xue, Q, Nagy, JA, Manseau, EJ, et al. Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking S6Kinase. Arterioscler Thromb Vasc Biol. 2009; 29, 11721178.
39.Wen, HY, Abbasi, S, Kellems, RE, Xia, Y. mTOR: a placental growth signaling sensor. Placenta. 2005; 26(Suppl. A), S63S69.
40.Xu, Y, Wang, Q, Cook, TJ, Knipp, GT. Effect of placental fatty acid metabolism and regulation by peroxisome proliferator activated receptor on pregnancy and fetal outcomes. J Pharm Sci. 2007; 96, 25822606.
41.Capobianco, E, White, V, Higa, R, Martinez, N, Jawerbaum, A. Effects of natural ligands of PPARgamma on lipid metabolism in placental tissues from healthy and diabetic rats. Mol Hum Reprod. 2008; 14, 491499.
42.Jarvie, E, Hauguel-de-Mouzon, S, Nelson, SM, et al. Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring. Clin Sci (Lond). 2010; 119, 123129.
43.Robillard, PY, Christon, R. Lipid intake during pregnancy in developing countries: possible effect of essential fatty acid deficiency on fetal growth. Prostaglandins Leukot Essent Fatty Acids. 1993; 48, 139142.
44.Amico, JA, Thomas, A, Crowley, RS, Burmeister, LA. Concentrations of leptin in the serum of pregnant, lactating, and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue. Life Sci. 1998; 63, 13871395.
45.Dessolin, S, Schalling, M, Champigny, O, et al. Leptin gene is expressed in rat brown adipose tissue at birth. FASEB J. 1997; 11, 382387.
46.Wlodek, ME, Westcott, KT, O'Dowd, R, et al. Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R1620R1627.
47.Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL, Gluckman, PD. Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. Am J Physiol Endocrinol Metab. 2000; 279, E83E87.
48.Burton, PJ, Waddell, BJ. 11 beta-Hydroxysteroid dehydrogenase in the rat placenta: developmental changes and the effects of altered glucocorticoid exposure. J Endocrinol. 1994; 143, 505513.
49.Lindsay, RS, Lindsay, RM, Waddell, BJ, Seckl, JR. Prenatal glucocorticoid exposure leads to offspring hyperglycaemia in the rat: studies with the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone. Diabetologia. 1996; 39, 12991305.
50.Moritz, KM, Johnson, K, Douglas-Denton, R, Wintour, EM, Dodic, M. Maternal glucocorticoid treatment programs alterations in the renin-angiotensin system of the ovine fetal kidney. Endocrinology. 2002; 143, 44554463.
51.Sloboda, DM, Newnham, JP, Challis, JR. Effects of repeated maternal betamethasone administration on growth and hypothalamic-pituitary-adrenal function of the ovine fetus at term. J Endocrinol. 2000; 165, 7991.
52.Fowden, AL, Ward, JW, Wooding, FP, Forhead, AJ, Constancia, M. Programming placental nutrient transport capacity. J Physiol. 2006; 572, 515.
53.Jansson, T, Cetin, I, Powell, TL, et al. Placental transport and metabolism in fetal overgrowth – a workshop report. Placenta. 2006; 27(Suppl. A), S109S113.
54.Jones, HN, Woollett, LA, Barbour, N, et al. High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice. FASEB J. 2009; 23, 271278.
55.Fowden, AL, Sferruzzi-Perri, AN, Coan, PM, Constancia, M, Burton, GJ. Placental efficiency and adaptation: endocrine regulation. J Physiol. 2009; 587, 34593472.
56.Fowden, AL, Forhead, AJ. Endocrine mechanisms of intrauterine programming. Reproduction. 2004; 127, 515526.
57.Mark, PJ, Smith, JT, Waddell, BJ. Placental and fetal growth retardation following partial progesterone withdrawal in rat pregnancy. Placenta. 2006; 27, 208214.

Keywords

A maternal high-fat diet in rat pregnancy reduces growth of the fetus and the placental junctional zone, but not placental labyrinth zone growth

  • P. J. Mark (a1), C. Sisala (a1), K. Connor (a2), R. Patel (a2), J. L. Lewis (a1), M. H. Vickers (a2), B. J. Waddell (a1) and D. M. Sloboda (a2)...

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