Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T12:58:12.517Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  07 January 2011

P. J. Mark*
Affiliation:
School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia, Australia
C. Sisala
Affiliation:
School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia, Australia
K. Connor
Affiliation:
The Liggins Institute and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand
R. Patel
Affiliation:
The Liggins Institute and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand
J. L. Lewis
Affiliation:
School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia, Australia
M. H. Vickers
Affiliation:
The Liggins Institute and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand
B. J. Waddell
Affiliation:
School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia, Australia
D. M. Sloboda
Affiliation:
The Liggins Institute and the National Research Centre for Growth and Development, The University of Auckland, Auckland, New Zealand
*
*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)

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.

Type
Original Articles
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Schrauwers, C, Dekker, G. Maternal and perinatal outcome in obese pregnant patients. J Matern Fetal Neonatal Med. 2009; 22, 218226.CrossRefGoogle ScholarPubMed
2.Ogden, CL, Carroll, MD, Curtin, LR, et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006; 295, 15491555.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
7.Mathew, M, Machado, L, Al-Ghabshi, R, Al-Haddabi, R. Fetal macrosomia. Risk factor and outcome. Saudi Med J. 2005; 26, 96100.Google ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
11.Barker, DJ. Fetal growth and adult disease. Br J Obstet Gynaecol. 1992; 99, 275276.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
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.CrossRefGoogle Scholar
15.Gagnon, R. Placental insufficiency and its consequences. Eur J Obstet Gynecol Reprod Biol. 2003; 110(Suppl. 1), S99S107.CrossRefGoogle ScholarPubMed
16.Jansson, T, Powell, TL. Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clin Sci (Lond). 2007; 113, 113.Google Scholar
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.Google Scholar
18.Wyrwoll, CS, Seckl, JR, Holmes, MC. Altered placental function of 11beta-hydroxysteroid dehydrogenase 2 knockout mice. Endocrinology. 2009; 150, 12871293.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
25.Roos, S, Powell, TL, Jansson, T. Placental mTOR links maternal nutrient availability to fetal growth. Biochem Soc Trans. 2009; 37, 295298.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
33.Snedecor, G, Cochrane, W. Statistical Methods 1989. Iowa State University Press: Ames, IA.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
39.Wen, HY, Abbasi, S, Kellems, RE, Xia, Y. mTOR: a placental growth signaling sensor. Placenta. 2005; 26(Suppl. A), S63S69.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
52.Fowden, AL, Ward, JW, Wooding, FP, Forhead, AJ, Constancia, M. Programming placental nutrient transport capacity. J Physiol. 2006; 572, 515.Google Scholar
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.Google Scholar
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.Google Scholar
55.Fowden, AL, Sferruzzi-Perri, AN, Coan, PM, Constancia, M, Burton, GJ. Placental efficiency and adaptation: endocrine regulation. J Physiol. 2009; 587, 34593472.Google Scholar
56.Fowden, AL, Forhead, AJ. Endocrine mechanisms of intrauterine programming. Reproduction. 2004; 127, 515526.Google Scholar
57.Mark, PJ, Smith, JT, Waddell, BJ. Placental and fetal growth retardation following partial progesterone withdrawal in rat pregnancy. Placenta. 2006; 27, 208214.CrossRefGoogle ScholarPubMed