Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-22T21:41:47.320Z Has data issue: false hasContentIssue false

The effect of docosahexaenoic acid and folic acid supplementation on placental apoptosis and proliferation

Published online by Cambridge University Press:  08 March 2007

Mario Klingler
Affiliation:
Dr von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany Clinic of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria
Astrid Blaschitz
Affiliation:
Institute of Cell BiologyHistology and Embryology, Medical University of Graz, Graz, Austria
Christina Campoy
Affiliation:
Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain
Ana Caño
Affiliation:
Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain
Anne M Molloy
Affiliation:
Department of Clinical Medicine,Trinity College Dublin, Republic of Ireland
John M Scott
Affiliation:
Department of Clinical Medicine,Trinity College Dublin, Republic of Ireland
Gottfried Dohr
Affiliation:
Institute of Cell BiologyHistology and Embryology, Medical University of Graz, Graz, Austria
Hans Demmelmair
Affiliation:
Dr von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
Berthold Koletzko
Affiliation:
Dr von Hauner Children's Hospital, Ludwig-Maximilians-University of Munich, Munich, Germany
Gernot Desoye*
Affiliation:
Clinic of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria
*
*Corresponding author: Dr Gernot Desoye, fax +43 316 385 2506, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The hypothesis was tested that the additional dietary uptake of n-3 fatty acids, in particular of DHA and 5-methyltetrahydrofolate (5-MTHF), during the second half of pregnancy would influence proliferation and apoptosis in the full-term human placenta. The diets of pregnant women from Spain (n 55) were supplemented with modified fish oil and/or 5-MTHF or placebo, and assigned in a random, double-blind manner to one of the four groups. Immunohistochemistry and immunoblotting were used to detect placental proliferation and apoptosis with monoclonal antibodies for key proteins that reflected the extent of both processes: proliferation cell nuclear antigen (PCNA), p53, cytokeratin 18 neoepitope. The PCNA level in the fish oil/5-MTHF-treated group was higher by 66% (P<0·05) than that of the placebo group, whereas the levels of p53 and cytokeratin 18 neoepitope were unaffected by treatment. PCNA expression was altered only in the trophoblast compartment (placebo 11·1 (se 0·5) % V. combination 21·5 (se 1·2) % P<0·05), whereas the proportion of nuclei stained in endothelial and other stromal cells was similar in the placebo and combined treatment groups. No correlation was found between fish oil or 5-MTHF supplementation and the levels of the proteins. The present data suggest that supplementation with fish oil and/or 5-MTHF had no effect on the parameters reflecting placental proliferation and apoptosis. A defined combination of DHA and 5-MTHF may, however, affect placental proliferation.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2006

References

Akbar, M & Kim, HYProtective effects of docosahexaenoic acid in staurosporine-induced apoptosis: involvement of phosphatidylinositol-3 kinase pathway. J Neurochem (2002) 82, 655665.CrossRefGoogle ScholarPubMed
Arnholdt, H, Meisel, F, Fandrey, K & Lohrs, UProliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies. Virchows Arch B Cell Pathol Incl Mol Pathol (1991) 60, 365372.CrossRefGoogle ScholarPubMed
Austgulen, R, Chedwick, L, Isaksen, CV, Vatten, L & Craven, CTrophoblast apoptosis in human placenta at term as detected by expression of a cytokeratin 18 degradation product of caspase. Arch Pathol Lab Med (2002) 126, 14801486.CrossRefGoogle ScholarPubMed
Black, S, Yu, H, Lee, J, Sachchithananthan, M & Medcalf, RLPhysiologic concentrations of magnesium and placental apoptosis: prevention by antioxidants. Obstet Gynecol (2001) 98, 319324.Google ScholarPubMed
Calviello, G, Palozza, P, Piccioni, E, Maggiano, N, Frattucci, A, Franceschelli, P & Bartoli, GMDietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis. Int J Cancer (1998) 75, 699705.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
Crocker, IP, Cooper, S, Ong, SC & Baker, PNDifferences in apoptotic susceptibility of cytotrophoblasts and syncytiotrophoblasts in normal pregnancy to those complicated with preeclampsia and intrauterine growth restriction. Am J Pathol (2003) 162, 637643.CrossRefGoogle ScholarPubMed
Desoye, G & Kaufmann, PThe human placenta in diabetes. In Diabetology of Pregnancy, pp. 94109 [Djelmis, J, Desoye, G and Ivanisevic, M, editors]. Basel: Karger. 2005Google Scholar
de Urquiza, AM, Liu, S, Sjoberg, M, Zetterstrom, RH, Griffiths, W, Sjovall, J & Perlmann, TDocosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science (2000) 290, 21402144.CrossRefGoogle ScholarPubMed
Ding, F, Fu, GQ, Xing, FQ, Chen, SL & Liu, YXEffect of abnormal apoptosis in human decidual tissue during early gestation on pregnancy. Di Yi Jun Yi Da Xue Xue Bao (Academic Journal of The First Medical College of PLA) (2002) 22, 145147.Google ScholarPubMed
Elmadfa, I, Erbersdobler, H, Gassmann, B, Stehle, P, Stehle, P & Wolfram, GReferenzwerte für die Nährstoffzufuhr (Reference Values for Nutrient Intake). [Deutsche Gesellschaft für Ernährung, Östereichische Gesellschaft für Ernährung, Schweizerische Gesellschaft für Ernährungsforschung and Schweizerische Vereinigung für Ernährung, editors]. Frankfurt am Main: Unschau Braus. 2000Google Scholar
Finstad, HS, Drevon, CA, Kulseth, MA, Synstad, AV, Knudsen, E & Kolset, SOCell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid. Biochem J (1998) 336, 451459.CrossRefGoogle ScholarPubMed
Gibson, RA, Neumann, MA & Makrides, MEffect of dietary docosahexaenoic acid on brain composition and neural function in term infants. Lipids (1996) 31, S177S181.CrossRefGoogle ScholarPubMed
Godfrey, KM & Barker, DJFetal nutrition and adult disease. Am J Clin Nutr (2000) 71, 1344S1352S.CrossRefGoogle ScholarPubMed
Gruslin, A, Qiu, Q & Tsang, BKInfluence of maternal smoking on trophoblast apoptosis throughout development: possible involvement of Xiap regulation. Biol Reprod (2001) 65, 11641169.CrossRefGoogle ScholarPubMed
Haidacher, S, Blaschitz, A, Desoye, G & Dohr, GImmunohistochemical evidence of p53 protein in human placenta and choriocarcinoma cell lines. Hum Reprod (1995) 10, 983988.CrossRefGoogle ScholarPubMed
Hay, WW JrPlacental transport of nutrients to the fetus. Horm Res (1994) 42, 215222.Google ScholarPubMed
Helland, IB, Saugstad, OD, Smith, L, Saarem, K, Solvoll, K, Ganes, T & Drevon, CASimilar effects on infants of n-3 and n-6 fatty acids supplementation to pregnant and lactating women. Pediatrics (2001) 108, E82.CrossRefGoogle ScholarPubMed
Huppertz, B, Kingdom, J, Caniggia, I, Desoye, G, Black, S, Korr, H & Kaufmann, PHypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta (2003) 24, 181190.CrossRefGoogle ScholarPubMed
Ishihara, N, Matsuo, H, Murakoshi, H, Laoag-Fernandez, J, Samoto, T & Maruo, TChanges in proliferative potential, apoptosis and Bcl-2 protein expression in cytotrophoblasts and syncytiotrophoblast in human placenta over the course of pregnancy. Endocr J (2000) 47, 317327.CrossRefGoogle ScholarPubMed
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PW & Rosenberg, IHThe effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med (1999) 340, 14491454.CrossRefGoogle ScholarPubMed
Klingler, M, Demmelmair, H, Larque, E & Koletzko, BAnalysis of FA contents in individual lipid fractions from human placental tissue. Lipids (2003) 38, 561566.CrossRefGoogle ScholarPubMed
Koletzko, B, Aggett, PJ, Bindels, JG, Bung, P, Ferre, P, Gil, A, Lentze, MJ, Roberfroid, M & Strobel, SGrowth, development and differentiation: a functional food science approach. Br J Nutr (1998) 80, Suppl. 1, S5S45.CrossRefGoogle ScholarPubMed
Kosanke, G, Kadyrov, M, Korr, H & Kaufmann, PMaternal anemia results in increased proliferation in human placental villi. Trophoblast Res (1998) 11, 339357.Google Scholar
Kurki, P, Ogata, K & Tan, EMMonoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immunol Methods (1988) 109, 4959.CrossRefGoogle ScholarPubMed
Leers, MPG, Kolgen, W, Bjorklund, V, Bergman, T, Tribbick, G, Persson, B, Bjorklund, P, Ramaekers, FCS, Bjorklund, B & Nap, MImmunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. J Pathol (1999) 187, 567572.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Lowry, O, Rosebrough, N, Farr, A & Randall, RProtein measurement with Folin-phenol reagent. J Biol Chem (1951) 193, 265275.CrossRefGoogle ScholarPubMed
Molloy, AM & Scott, JMMicrobiological assay for serum, plasma, and red blood cell folate using cryopreserved, microtiter plate method. Meth Enzymol (1997) 281, 4345.CrossRefGoogle ScholarPubMed
Montgomery, C, Speake, BK, Cameron, A, Sattar, N & Weaver, LTMaternal docosahexaenoic acid supplementation and fetal accretion. Br J Nutr (2003) 90, 135145.CrossRefGoogle ScholarPubMed
Myatt, LRole of placenta in preeclampsia. Endocrine (2002) 19, 103111.CrossRefGoogle ScholarPubMed
Narayanan, BA, Narayanan, NK & Reddy, BSDocosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Int J Oncol (2001) 19, 12551262.Google ScholarPubMed
Olsen, SF, Sorensen, JD, Secher, NJ, Hedegaard, M, Henriksen, TB, Hansen, HS & Grant, ARandomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet (1992) 339, 10031007.CrossRefGoogle ScholarPubMed
Osmond, C & Barker, DJFetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ Health Perspect (2000) 108, Suppl. 3, 545553.Google ScholarPubMed
Paunesku, T, Mittal, S, Proticacute, M, Oryhon, J, Korolev, SV, Joachimiak, A & Woloschak, GEProliferating cell nuclear antigen (PCNA): ringmaster of the genome. Int J Radiat Biol (2001) 77, 10071021.CrossRefGoogle ScholarPubMed
Polliotti, BM, Abramowsky, C, Schwartz, DA, Keesling, SS, Lee, GR, Caba, J, Zhang, W, Panigel, M & Nahmias, AJCulture of first-trimester and full-term human chorionic villus explants: role of human chorionic gonadotropin and human placental lactogen as a viability index. Early Pregnancy (1995) 1, 270280.Google ScholarPubMed
Rodriguez, A, Raederstorff, D, Sarda, P, Lauret, C, Mendy, F & Descomps, BPreterm infant formula supplementation with a-linolenic acid and docosahexaenoic acid. Eur J Clin Nutr (2003) 57, 727734.CrossRefGoogle Scholar
Rudolph, IL, Kelley, DS, Klasing, KC & Erickson, KLRegulation of cellular differentiation and apoptosis by fatty acids and their metabolites. Nutr Res (2001) 21, 381393.CrossRefGoogle ScholarPubMed
Scholl, TO & Johnson, WGFolic acid: influence on the outcome of pregnancy. Am J Clin Nutr (2000) 1295S1303S.CrossRefGoogle ScholarPubMed
Smith, SC, Baker, PN & Symonds, EMPlacental apoptosis in normal human pregnancy. Am J Obstet Gynecol (1997) 177, 5765.CrossRefGoogle ScholarPubMed
Smuts, CM, Huang, M, Mundy, D, Plasse, T, Major, S & Carlson, SEA randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy. Obstet Gynecol (2003) 101, 469479.Google ScholarPubMed
Steegers-Theunissen, RP, Smith, SC, Steegers, EA, Guilbert, LJ & Baker, PNFolate affects apoptosis in human trophoblastic cells. Br J Obstet Gynaecol (2000) 107, 15131515.CrossRefGoogle ScholarPubMed
van Houwelingen, AC, Sorensen, JD, Hornstra, G, Simonis, MM, Boris, J, Olsen, SF & Secher, NJEssential fatty acid status in neonates after fish-oil supplementation during late pregnancy. Br J Nutr (1995) 74, 723731.CrossRefGoogle ScholarPubMed
von Kries, R, Koletzko, B, Sauerwald, T, von Mutius, E, Barnert, D, Grunert, V & von Voss, HBreast feeding and obesity: cross sectional study. Br Med J (1999) 319, 147150.CrossRefGoogle ScholarPubMed
Waterland, RA & Garza, CPotential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr (1999) 69, 179197.CrossRefGoogle ScholarPubMed
Yano, M, Kishida, E, Iwasaki, M, Kojo, S & Masuzawa, YDocosahexaenoic acid and vitamin E can reduce human monocytic U937 cell apoptosis induced by tumor necrosis factor. J Nutr (2000) 130, 10951101.CrossRefGoogle ScholarPubMed