Maternal–Fetal Cholesterol Transport in the Placenta
2009; Lippincott Williams & Wilkins; Volume: 104; Issue: 5 Linguagem: Inglês
10.1161/circresaha.109.194191
ISSN1524-4571
Autores Tópico(s)Peroxisome Proliferator-Activated Receptors
ResumoHomeCirculation ResearchVol. 104, No. 5Maternal–Fetal Cholesterol Transport in the Placenta Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBMaternal–Fetal Cholesterol Transport in the PlacentaGood, Bad, and Target for Modulation Wulf Palinski Wulf PalinskiWulf Palinski From the Department of Medicine, University of California San Diego. Originally published13 Mar 2009https://doi.org/10.1161/CIRCRESAHA.109.194191Circulation Research. 2009;104:569–571The transport of cholesterol from mother to fetus across the placental barrier has long been neglected. Although cholesterol is of vital importance for fetal development as a key constituent of cell membranes, precursor of steroid hormones and metabolic regulators (oxysterols), and a modulator of hedgehog signaling, it was generally assumed that most of it is synthesized de novo by the fetus and, to a lesser extent, by cells on the fetal side of the placenta. A contribution of placental cholesterol to fetal growth was supported by the fact that LDL-cholesterol concentrations in the umbilical cord vein (which delivers placental blood to the fetus) are greater than those in umbilical arteries,1 and by the ability of placental cells to secrete apolipoprotein (apo)B-containing particles.2 On the other hand, the case against maternal cholesterol transfer was based on the observation that the placental barrier is impermeable to labeled LDL and other lipoprotein particles and that genetically normal offspring of hypercholesterolemic mothers generally have very low cholesterol levels at term birth, whereas maternal cholesterol tends to be highest in the third trimester.Given the essential role of independent cholesterol synthesis, it is not surprising that most of the known genetic defects of cholesterol biosynthesis in fetuses severely impact their development and survival. The one exception is the Smith–Lemli–Opitz syndrome (SLO), a defect in the conversion of 7-dihydrocholesterol to cholesterol.3 Children with SLO are born relatively healthy and must therefore have obtained a minimum of cholesterol from the mother. Interest in potential mechanisms transporting cholesterol from mother to fetus was further stimulated by the recognition that maternal hypercholesterolemia, even if limited to pregnancy, markedly promotes the formation of fatty streaks in human fetal aortas4 and leads to increased susceptibility to atherosclerosis later in life.5,6 Investigations of developmental programming of cardiovascular disease also revealed that fetal cholesterol levels are much higher in midpregnancy than at term birth and correlate with maternal cholesterol before the sixth month of gestation, consistent with transplacental cholesterol passage.4,7In humans, maternal cholesterol must cross 2 barriers to reach the fetal circulation (Figure). First, from the blood-filled lacunae surrounding the chorionic villi it has to enter the apical side of the multinucleated cells of the syncytiotrophoblast and be secreted on their basolateral side. Second, it must be transported across the endothelial cells of the fetal microvessels. To date, it has been established that cultured trophoblast cells express LDL receptors (LDLR), LDLR-related proteins (LRP), scavenger receptors A (SR-A), and HDL-binding scavenger receptors B1 (SR-B1) on their apical side.8 Cholesterol taken up by internalization of receptor-bound apoB- or apoE-carrying lipoproteins and oxidized LDL, and from SR-B1-bound HDL, is then released on the basolateral side.8 Uptake of cholesterol by endothelial cells is well understood, but the mechanisms by which placental endothelial cells transport cholesterol to the fetal microcirculation, the regulation of efflux, and their ability to deliver substantial quantities of cholesterol were unknown. In this issue of Circulation Research, an article by Stefulj et al fills this important gap and not only elucidates the final link in the maternal–fetal cholesterol transport mechanism but also indicates how it may be regulated (Figure).9Download figureDownload PowerPointFigure. Maternal-fetal cholesterol transport in the placenta.By comparing cholesterol export mechanisms in human placental endothelial cells (HPECs) to those of human umbilical vein endothelial cells (HUVECs), the authors show that HPECs released significantly more cholesterol to lipid-free apoA-I, whereas both cell types delivered similar amounts of cholesterol to HDL. Furthermore, exposure of HPECs, but not HUVECs, to natural or synthetic ligands of liver-X-receptors (LXR) increased cholesterol efflux to both of these acceptors. LXR activation increased expression of ABCA1 and ABCG1 but did not alter that of ABCG4 and SR-BI. Conversely, inhibition of ABCA1 or silencing of ABCG1 markedly decreased cholesterol efflux to apoA-I and HDL. Cholesterol efflux from LXR-stimulated HPECs to HDL via ABCG1 was further increased when HDL was enriched with apoE. Immunohistochemistry confirmed that ABCA1 and ABCG1 were mainly, if not exclusively, expressed on the luminal (fetal) side of HPECs, consistent with its selective role in cholesterol efflux toward the fetal circulation. Together, these data establish that HPECs are unique among endothelial cells, in so far as they are capable of transporting substantial amounts of cholesterol to the fetal circulation, and that this mechanism is further increased by LXR-induced upregulation of ABCA1 and ABCG1.An experiment mimicking the placenta in mothers developing extensive hypercholesterolemia during pregnancy (by preloading HPECs with LDL or cholesterol) confirmed that HPECs are not just capable of transferring markedly more cholesterol to the fetus but that they actually do so under conditions similar to those encountered in vivo, provided that enough acceptors are present. This, however, was not accompanied by an upregulation of ABCA1 and ABCG1 (except for a modest induction of the latter by cholesterol-loading only). As the authors explain, other regulatory factors must be involved. This prompts some thoughts about the role of maternal–fetal cholesterol transport and its in vivo regulation throughout pregnancy (Figure, right side).We have to presume that the basic machinery of HPECs isolated at term birth is representative of placental endothelial cells throughout pregnancy and that gestational age does not affect function, but we do know that the placental conditions undergo dramatic temporal changes throughout pregnancy. For example, maternal cholesterol levels increase in the third trimester, even in normocholesterolemic mothers, whereas fetal cholesterol is exceedingly high at the end of the second trimester and then declines linearly toward term.4 Even in the absence of maternal hypercholesterolemia, oxidative stress is therefore bound to vary greatly, as are lipid peroxidation products, such as oxidized LDL, oxidized fatty acids, and reactive oxygen species (ROS), which interfere with several oxidation-sensitive nuclear signaling pathways, including nuclear factor κB, peroxisome proliferator-activated receptor,10 and, indirectly, LXR11,12 (at least in macrophages). Thus, both the regulation and the extent of maternal–fetal cholesterol transport are likely to undergo substantial physiological variation throughout pregnancy.In fetuses with SLO, there is a vital dependence on maternal cholesterol that must be satisfied irrespective of the maternal cholesterol level. The greatest regulatory stimulus therefore probably comes from the fetal side, in the form of increased plasma levels of cholesterol acceptors and LXR activation. Both major natural LXR activators, 24S- and 27OH-cholesterol, are present in the fetal circulation and elevated in SLO, suggesting that LXR-mediated upregulation of ABCA1 and ABCG1 indeed contributes to increase cholesterol transfer in vivo. Maternal dietary cholesterol supplementation also appears to convey benefits to SLO fetuses.13 This is consistent with the present observation in cholesterol and LDL-enriched HPECs (Figure 5B and 5C in the article by Stefulj et al9) and suggests that signaling by increased maternal cholesterol may be beneficial in the presence of synergistic fetal signals.In contrast, extensive maternal hypercholesterolemia alone is clearly pathogenic and results in atherogenic programming.5,6 The present data indicate that increased cholesterol availability on the maternal side substantially increases transfer, consistent with results in humans and animal models,4,6,14 but that no significant upregulation of LXR occurs in the absence of fetal costimuli. This is a relief, because it indicates that maternal hypercholesterolemia does not automatically trigger maximum upregulation of cholesterol transport. Signaling in HPECs of hypercholesterolemic mothers appears to be influenced by additional factors, some of which may be compensatory/defensive. In fact, studies in humans have shown that the placenta is both the target of maternal oxidative stress and a modulator of fetal oxidative stress.15 Furthermore, extensive data exist on atherogenic programming of arterial endothelial cells by maternal hypercholesterolemia, obesity, the metabolic syndrome, and diabetes.16,17 It is therefore likely that changes in HPEC signaling are similarly early and extensive.Fortunately, atherogenic programming in offspring of hypercholesterolemic mothers can be prevented by interventions reducing fetal exposure to maternal hypercholesterolemia and oxidative stress,6,14 including by targeted maternal immunostimulation.18 It would be interesting to see whether such interventions also influence signaling in HPECs and, conversely, whether targeting of HEPC signaling protects offspring against atherogenic programming.The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.Sources of FundingSupported by National Heart, Lung, and Blood Institute grant R01-HL-089559 and Ellison Medical Foundation Senior Scholar Award AG-SS 1851-07.DisclosuresNone.FootnotesCorrespondence to Wulf Palinski, MD, FRCP, University of California, San Diego, Department of Medicine 0682, 9500 Gilman Dr, La Jolla, CA 92093-0682. E-mail [email protected] References 1 Parker CR Jr, Deahl T, Drewry P, Hankins G. Analysis of the potential for transfer of lipoprotein-cholesterol across the human placenta. Early Hum Dev. 1983; 8: 289–295.CrossrefMedlineGoogle Scholar2 Madsen EM, Lindegaard ML, Andersen CB, Damm P, Nielsen LB. Human placenta secretes apolipoprotein B-100-containing lipoproteins. J Biol Chem. 2004; 279: 55271–55276.CrossrefMedlineGoogle Scholar3 Tint GS, Irons M, Elias ER, Batta AK, Frieden R, Chen TS, Salen G. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994; 330: 107–113.CrossrefMedlineGoogle Scholar4 Napoli C, D'Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, Palinski W. 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: 2680–2690.CrossrefMedlineGoogle Scholar5 Napoli C, Glass CK, Witztum JL, Deutsch R, D'Armiento FP, Palinski W. Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study. Lancet. 1999; 354: 1234–1241.CrossrefMedlineGoogle Scholar6 Palinski W, D'Armiento FP, Witztum JL, de Nigris F, Casanada F, Condorelli M, Silvestre M, Napoli C. Maternal hypercholesterolemia and treatment during pregnancy influence the long-term progression of atherosclerosis in offspring of rabbits. Circ Res. 2001; 89: 991–996.CrossrefMedlineGoogle Scholar7 Woollett LA. The origins and roles of cholesterol and fatty acids in the fetus. Curr Opin Lipidol. 2001; 12: 305–312.CrossrefMedlineGoogle Scholar8 Woollett LA. Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation. Am J Clin Nutr. 2005; 82: 1155–1161.CrossrefMedlineGoogle Scholar9 Stefulj J, Panzenboeck U, Becker T, Hirschmugl B, Schweinzer C, Lang I, Marsche G, Sadjak A, Lang U, Desoye G, Wadsack C. Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circ Res. 2009; 104: 600–608.LinkGoogle Scholar10 Barish GD, Narkar VA, Evans RM. PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest. 2006; 116: 590–597.CrossrefMedlineGoogle Scholar11 Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, Liao D, Nagy L, Edwards PA, Curtiss LK, Evans RM, Tontonoz P. A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell. 2001; 7: 161–171.CrossrefMedlineGoogle Scholar12 Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, Laffitte BA, Chen M, Noh G, Goodman J, Hagger GN, Tran J, Tippin TK, Wang X, Lusis AJ, Hsueh WA, Law RE, Collins JL, Willson TM, Tontonoz P. Synthetic LXR ligand inhibits the development of atherosclerosis in mice. Proc Natl Acad Sci U S A. 2002; 99: 7604–7609.CrossrefMedlineGoogle Scholar13 Elias ER, Irons MB, Hurley AD, Tint GS, Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS). Am J Med Genet. 1997; 68: 305–310.CrossrefMedlineGoogle Scholar14 Napoli C, Witztum JL, Calara F, de Nigris F, Palinski W. Maternal hypercholesterolemia enhances atherogenesis in normocholesterolemic rabbits, which is inhibited by antioxidant or lipid-lowering intervention during pregnancy: an experimental model of atherogenic mechanisms in human fetuses. Circ Res. 2000; 87: 946–952.CrossrefMedlineGoogle Scholar15 Liguori A, D'Armiento FP, Palagiano A, Balestrieri ML, Williams-Ignarro S, de Nigris F, Lerman LO, D'Amora M, Rienzo M, Fiorito C, Ignarro LJ, Palinski W, Napoli C. Effect of gestational hypercholesterolaemia on omental vasoreactivity, placental enzyme activity and transplacental passage of normal and oxidised fatty acids. BJOG. 2007; 114: 1547–1556.CrossrefMedlineGoogle Scholar16 Poston L. Influences of maternal nutritional status on vascular function in the offspring. Curr Drug Targets. 2007; 8: 914–922.CrossrefMedlineGoogle Scholar17 Palinski W, Napoli C. Impaired fetal growth, cardiovascular disease, and the need to move on. Circulation. 2008; 117: 341–343.LinkGoogle Scholar18 Yamashita T, Freigang S, Eberle C, Pattison J, Gupta S, Napoli C, Palinski W. Maternal immunization programs postnatal immune responses and reduces atherosclerosis in offspring. Circ Res. 2006; 99: e51–e64.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Sethuraman V, Pu Y, Gingrich J, Jing J, Long R, Olomu I and Veiga-Lopez A (2022) Expression of ABC transporters during syncytialization in preeclampsia, Pregnancy Hypertension, 10.1016/j.preghy.2022.01.006, 27, (181-188), Online publication date: 1-Mar-2022. Mauri M, Calmarza P and Ibarretxe D (2021) Dyslipemias and pregnancy, an update, Clínica e Investigación en Arteriosclerosis (English Edition), 10.1016/j.artere.2020.12.005, 33:1, (41-52), Online publication date: 1-Jan-2021. Mauri M, Calmarza P and Ibarretxe D (2021) Dislipemias y embarazo, una puesta al día, Clínica e Investigación en Arteriosclerosis, 10.1016/j.arteri.2020.10.002, 33:1, (41-52), Online publication date: 1-Jan-2021. Fang F, Nuyt A, Garofalo C, Zhang J, Julien P, Fraser W, Levy E and Luo Z (2021) Oxidized LDL, insulin sensitivity and beta-cell function in newborns, BMJ Open Diabetes Research & Care, 10.1136/bmjdrc-2020-001435, 9:1, (e001435), Online publication date: 1-Mar-2021. Wang H, Liang N, Huang D, Zhao X, Dang Q, Jiang X, Xiao R and Yu H (2021) The effects of high-density lipoprotein and oxidized high-density lipoprotein on forskolin-induced syncytialization of BeWo cells, Placenta, 10.1016/j.placenta.2020.10.024, 103, (199-205), Online publication date: 1-Jan-2021. Cai X, Liang N, Wang H, Gao A, Xiao R and Yu H (2020) Lipidomic profiles of maternal blood at the earlier stage of gestation and umbilical venous blood in response to supraphysiological hypercholesterolemia versus physiological hypercholesterolemia: An evidence of potential biomarkers and early intervention, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 10.1016/j.bbalip.2019.158587, 1865:3, (158587), Online publication date: 1-Mar-2020. Kallol S and Albrecht C (2020) Materno-fetal cholesterol transport during pregnancy, Biochemical Society Transactions, 10.1042/BST20190129, 48:3, (775-786), Online publication date: 30-Jun-2020. Fraichard C, Bonnet F, Garnier A, Hébert-Schuster M, Bouzerara A, Gerbaud P, Ferecatu I, Fournier T, Hernandez I, Trabado S and Guibourdenche J (2020) Placental production of progestins is fully effective in villous cytotrophoblasts and increases with the syncytiotrophoblast formation, Molecular and Cellular Endocrinology, 10.1016/j.mce.2019.110586, 499, (110586), Online publication date: 1-Jan-2020. Cantin C, Fuenzalida B and Leiva A (2020) Maternal hypercholesterolemia during pregnancy: Potential modulation of cholesterol transport through the human placenta and lipoprotein profile in maternal and neonatal circulation, Placenta, 10.1016/j.placenta.2020.03.007, 94, (26-33), Online publication date: 1-May-2020. Nasioudis D, Doulaveris G and Kanninen T Dyslipidemia in pregnancy and maternal-fetal outcome, Minerva Ginecologica, 10.23736/S0026-4784.18.04330-7, 71:2 Fuenzalida B, Sobrevia B, Cantin C, Carvajal L, Salsoso R, Gutiérrez J, Contreras-Duarte S, Sobrevia L and Leiva A (2018) Maternal supraphysiological hypercholesterolemia associates with endothelial dysfunction of the placental microvasculature, Scientific Reports, 10.1038/s41598-018-25985-6, 8:1, Online publication date: 1-Dec-2018. Hanna E, Simonelli S, Chamney S, Ossoli A and Mullan R (2018) Paradoxical fall in proteinuria during pregnancy in an LCAT-deficient patient—A case report, Journal of Clinical Lipidology, 10.1016/j.jacl.2018.06.006, 12:5, (1151-1156), Online publication date: 1-Sep-2018. Rodríguez M, García-García R, Arias-Álvarez M, Formoso-Rafferty N, Millán P, López-Tello J, Lorenzo P, González-Bulnes A and Rebollar P (2017) A diet supplemented with n-3 polyunsaturated fatty acids influences the metabomscic and endocrine response of rabbit does and their offspring1, Journal of Animal Science, 10.2527/jas.2017.1429, 95:6, (2690-2700), Online publication date: 1-Jun-2017. Farias D, Poston L, Franco-Sena A, Moura da Silva A, Pinto T, de Oliveira L and Kac G (2017) Maternal lipids and leptin concentrations are associated with large-for-gestational-age births: a prospective cohort study, Scientific Reports, 10.1038/s41598-017-00941-y, 7:1, Online publication date: 1-Dec-2017. Herrera E and Lasunción M (2017) Maternal-Fetal Transfer of Lipid Metabolites Fetal and Neonatal Physiology, 10.1016/B978-0-323-35214-7.00034-2, (342-353.e4), . Wild R, Weedin E and Wilson D (2016) Dyslipidemia in Pregnancy, Endocrinology and Metabolism Clinics of North America, 10.1016/j.ecl.2015.09.004, 45:1, (55-63), Online publication date: 1-Mar-2016. Leiva A, Fuenzalida B, Westermeier F, Toledo F, Salomón C, Gutiérrez J, Sanhueza C, Pardo F and Sobrevia L (2016) Role for Tetrahydrobiopterin in the Fetoplacental Endothelial Dysfunction in Maternal Supraphysiological Hypercholesterolemia, Oxidative Medicine and Cellular Longevity, 10.1155/2016/5346327, 2016, (1-10), . Prabhu A, Luu W, Li D, Sharpe L and Brown A (2016) DHCR7: A vital enzyme switch between cholesterol and vitamin D production, Progress in Lipid Research, 10.1016/j.plipres.2016.09.003, 64, (138-151), Online publication date: 1-Oct-2016. Wild R, Weedin E and Wilson D (2015) Dyslipidemia in Pregnancy, Cardiology Clinics, 10.1016/j.ccl.2015.01.002, 33:2, (209-215), Online publication date: 1-May-2015. Nelissen E, Dumoulin J, Busato F, Ponger L, Eijssen L, Evers J, Tost J and van Montfoort A (2014) Altered gene expression in human placentas after IVF/ICSI, Human Reproduction, 10.1093/humrep/deu241, 29:12, (2821-2831), Online publication date: 1-Dec-2014., Online publication date: 1-Dec-2014. Torres-Rovira L, Astiz S, Gonzalez-Añover P, Pallares P, Perez-Garnelo S, Perez-Solana M, Sanchez-Sanchez R and Gonzalez-Bulnes A (2014) Intake of high saturated-fat diets disturbs steroidogenesis, lipid metabolism and development of obese-swine conceptuses from early-pregnancy stages, The Journal of Steroid Biochemistry and Molecular Biology, 10.1016/j.jsbmb.2013.01.004, 139, (130-137), Online publication date: 1-Jan-2014. El-Sayyad H, Al-Haggar M, El-Ghawet H and Bakr I (2014) Effect of maternal diabetes and hypercholesterolemia on fetal liver of albino Wistar rats, Nutrition, 10.1016/j.nut.2013.08.016, 30:3, (326-336), Online publication date: 1-Mar-2014. Libby P (2013) Atherosclerosis Vascular Medicine: A Companion to Braunwald's Heart Disease, 10.1016/B978-1-4377-2930-6.00008-2, (111-125), . Houde A, Guay S, Desgagné V, Hivert M, Baillargeon J, St-Pierre J, Perron P, Gaudet D, Brisson D and Bouchard L (2014) Adaptations of placental and cord blood ABCA1 DNA methylation profile to maternal metabolic status , Epigenetics, 10.4161/epi.26554, 8:12, (1289-1302), Online publication date: 1-Dec-2013. Baumann M, Körner M, Huang X, Wenger F, Surbek D and Albrecht C (2013) Placental ABCA1 and ABCG1 expression in gestational disease: Pre-eclampsia affects ABCA1 levels in syncytiotrophoblasts, Placenta, 10.1016/j.placenta.2013.06.309, 34:11, (1079-1086), Online publication date: 1-Nov-2013. Kwiterovich P, Virgil D, Chu A, Khouzami V, Alaupovic P and Otvos J (2013) Interrelationships between the concentration and size of the largest high-density lipoprotein subfraction and apolipoprotein C-I in infants at birth and follow-up at 2–3 months of age and their parents, Journal of Clinical Lipidology, 10.1016/j.jacl.2012.09.002, 7:1, (29-37), Online publication date: 1-Jan-2013. Joo J, Hiden U, Lassance L, Gordon L, Martino D, Desoye G and Saffery R (2013) Variable promoter methylation contributes to differential expression of key genes in human placenta-derived venous and arterial endothelial cells, BMC Genomics, 10.1186/1471-2164-14-475, 14:1, Online publication date: 1-Dec-2013. Dowling O, Chatterjee P, Gupta M, Tam Tam H, Xue X, Lewis D, Rochelson B and Metz C (2012) Magnesium sulfate reduces bacterial LPS-induced inflammation at the maternal–fetal interface, Placenta, 10.1016/j.placenta.2012.01.013, 33:5, (392-398), Online publication date: 1-May-2012. Bartels Ä, Egan N, Broadhurst D, Khashan A, Joyce C, Stapleton M, O'Mullane J and O'Donoghue K (2012) Maternal serum cholesterol levels are elevated from the 1st trimester of pregnancy: A cross-sectional study, Journal of Obstetrics and Gynaecology, 10.3109/01443615.2012.714017, 32:8, (747-752), Online publication date: 1-Nov-2012. Gonzalez-Bulnes A, Ovilo C, Lopez-Bote C, Astiz S, Ayuso M, Perez-Solana M, Sanchez-Sanchez R and Torres-Rovira L Gender-specific early postnatal catch-up growth after intrauterine growth retardation by food restriction in swine with obesity/leptin resistance, REPRODUCTION, 10.1530/REP-12-0105, 144:2, (269-278) Seneff S, Davidson R and Mascitelli L (2012) Might cholesterol sulfate deficiency contribute to the development of autistic spectrum disorder?, Medical Hypotheses, 10.1016/j.mehy.2011.10.026, 78:2, (213-217), Online publication date: 1-Feb-2012. Gonzalez-Bulnes A, Torres-Rovira L, Ovilo C, Astiz S, Gomez-Izquierdo E, Gonzalez-Añover P, Pallares P, Perez-Solana M and Sanchez-Sanchez R (2012) Reproductive, endocrine and metabolic feto-maternal features and placental gene expression in a swine breed with obesity/leptin resistance, General and Comparative Endocrinology, 10.1016/j.ygcen.2011.12.038, 176:1, (94-101), Online publication date: 1-Mar-2012. Bartels Ä and O'Donoghue K (2011) Cholesterol in pregnancy: a review of knowns and unknowns, Obstetric Medicine, 10.1258/om.2011.110003, 4:4, (147-151), Online publication date: 1-Dec-2011. Quehenberger O, Yamashita T, Armando A, Dennis E and Palinski W (2011) Effect of gestational hypercholesterolemia and maternal immunization on offspring plasma eicosanoids, American Journal of Obstetrics and Gynecology, 10.1016/j.ajog.2011.03.044, 205:2, (156.e15-156.e25), Online publication date: 1-Aug-2011. Nikitina L, Wenger F, Baumann M, Surbek D, Körner M and Albrecht C (2011) Expression and localization pattern of ABCA1 in diverse human placental primary cells and tissues, Placenta, 10.1016/j.placenta.2011.03.003, 32:6, (420-430), Online publication date: 1-Jun-2011. Palinski W, Nicolaides E, Liguori A and Napoli C (2009) Influence of Maternal Dysmetabolic Conditions During Pregnancy on Cardiovascular Disease, Journal of Cardiovascular Translational Research, 10.1007/s12265-009-9108-7, 2:3, (277-285), Online publication date: 1-Sep-2009. Zhang R, Dong S, Ma W, Cai X, Le Z, Xiao R, Zhou Q, Yu H and Chan K (2017) Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta, PLOS ONE, 10.1371/journal.pone.0171934, 12:2, (e0171934) Nava-Salazar S, Flores-Pliego A, Pérez-Martínez G, Parra-Hernández S, Vanoye-Carlo A, Ibarguengoitia-Ochoa F, Perichart-Perera O, Reyes-Muñoz E, Solis-Paredes J, Espino y Sosa S and Estrada-Gutierrez G (2022) Resistin Modulates Low-Density Lipoprotein Cholesterol Uptake in Human Placental Explants via PCSK9, Reproductive Sciences, 10.1007/s43032-022-00943-w Hyanek J, Pehal F, Dryahina K, Dubska L and Míkova B (2019) Gestational hypercholesterolemia helps detect familial hypercholesterolemia and prevent late pregnancy complications, Clinical Journal of Obstetrics and Gynecology, 10.29328/journal.cjog.1001026, 2:2, (079-089) Shahnawaz S, Nawaz U, Zaugg J, Hussain G, Malik N, Dogar M, Malik S and Albrecht C (2021) Dysregulated Autophagy Leads to Oxidative Stress and Aberrant Expression of ABC Transporters in Women with Early Miscarriage, Antioxidants, 10.3390/antiox10111742, 10:11, (1742) Gonzalez-Bulnes A, Torres-Rovira L, Astiz S, Ovilo C, Sanchez-Sanchez R, Gomez-Fidalgo E, Perez-Solana M, Martin-Lluch M, Garcia-Contreras C, Vazquez-Gomez M and Kanellopoulos-Langevin C (2015) Fetal Sex Modulates Developmental Response to Maternal Malnutrition, PLOS ONE, 10.1371/journal.pone.0142158, 10:11, (e0142158) Bischoff S, Tsai S, Hardison N, Motsinger-Reif A, Freking B, Nonneman D, Rohrer G, Piedrahita J and Zhao S (2013) Differences in X-Chromosome Transcriptional Activity and Cholesterol Metabolism between Placentae from Swine Breeds from Asian and Western Origins, PLoS ONE, 10.1371/journal.pone.0055345, 8:1, (e55345) Garcia-Contreras C, Vazquez-Gomez M, Astiz S, Torres-Rovira L, Sanchez-Sanchez R, Gomez-Fidalgo E, Gonzalez J, Isabel B, Rey A, Ovilo C and Gonzalez-Bulnes A (2017) Ontogeny of Sex-Related Differences in Foetal Developmental Features, Lipid Availability and Fatty Acid Composition, International Journal of Molecular Sciences, 10.3390/ijms18061171, 18:6, (1171) Ayuso M, Fernández A, Núñez Y, Benítez R, Isabel B, Barragán C, Fernández A, Rey A, Medrano J, Cánovas Á, González-Bulnes A, López-Bote C, Ovilo C and PENA i SUBIRÀ R (2015) Comparative Analysis of Muscle Transcriptome between Pig Genotypes Identifies Genes and Regulatory Mechanisms Associated to Growth, Fatness and Metabolism, PLOS ONE, 10.1371/journal.pone.0145162, 10:12, (e0145162) Pesántez-Pacheco J, Heras-Molina A, Torres-Rovira L, Sanz-Fernández M, García-Contreras C, Vázquez-Gómez M, Feyjoo P, Cáceres E, Frías-Mateo M, Hernández F, Martínez-Ros P, González-Martin J, González-Bulnes A and Astiz S (2019) Maternal Metabolic Demands Caused by Pregnancy and Lactation: Association with Productivity and Offspring Phenotype in High-Yielding Dairy Ewes, Animals, 10.3390/ani9060295, 9:6, (295) Matata B (2016) Prenatal Nutritional High Fat Environment and the Evolving Concept of Intergenerational Cardio-Metabolic Disease Risk, MOJ Surgery, 10.15406/mojs.2016.03.00040, 3:2 GÜLÜCÜ S, ÇELİK S, SOYER ÇALIŞKAN C and ÇELİK S (2022) İlk Trimester Serum Lipid Profili ile Postterm Gebelik İlişkisi, Online Türk Sağlık Bilimleri Dergisi, 10.26453/otjhs.980463 March 13, 2009Vol 104, Issue 5 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCRESAHA.109.194191PMID: 19286612 Originally publishedMarch 13, 2009 Keywordsendothelial cellsplacentadevelopmental programmingarteriosclerosischolesterol transportPDF download Advertisement
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