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Effects of folic acid and vitamin B12 supplements on folate and homocysteine metabolism in pigs during early pregnancy

Published online by Cambridge University Press:  09 March 2007

Frédéric Guay ,
J. Jacques Matte ,
Christiane L. Girard ,
Marie-France Palin ,
Alain Giguère  and
Jean-Paul Laforest
Frédéric Guay
Affiliation:
Department of Animal Sciences and Centre de Recherche en Biologie de la Reproduction (CRBR), Laval University, Ste-Foy, Québec, Canada G1K 7P4
J. Jacques Matte*
Affiliation:
Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Lennoxville, Québec, Canada J1M 1Z3
Christiane L. Girard
Affiliation:
Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Lennoxville, Québec, Canada J1M 1Z3
Marie-France Palin
Affiliation:
Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Lennoxville, Québec, Canada J1M 1Z3
Alain Giguère
Affiliation:
Dairy and Swine Research and Development Centre, Agriculture and Agri-Food Canada, Lennoxville, Québec, Canada J1M 1Z3
Jean-Paul Laforest
Affiliation:
Department of Animal Sciences and Centre de Recherche en Biologie de la Reproduction (CRBR), Laval University, Ste-Foy, Québec, Canada G1K 7P4
*
*Corresponding author:Dr J. Jaques Matte, present address, Agriculture and Agri-Food Canada, 2000 route 108, CP 90 Lennoxville, Quebec, Canada J1M 1Z3, fax +819 564 5507, email mattej@em.agr.ca
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Abstract

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The present experiment aimed to determine the effects of supplements of folic acid (FA) alone or in combination with vitamin B12 on folate and homocysteine metabolism in gestating nulliparous Yorkshire–Landrace (YL) and multiparous Landrace (LD) occidental sows and multiparous Chinese Meishan–Landrace (ML) sows. LD sows were randomly assigned to two treatments: 0 or 15 mg FA/kg diet while YL and ML sows were assigned to three treatments: 0 mg FA/kg diet, 15 mg FA/kg or 15 mg FA+160 μg vitamin B12/kg diet. Supplements were given from the oestrus preceding insemination up to slaughter on day 15 of gestation. At slaughter, a uterine flush was collected to determine uterine contents of homocysteine, methionine, tetrahydrofolate (THF), 5-methyl-THF, pyridoxal 5-phosphate (P5P) and vitamin B12. Blood samples were taken at first oestrus, at insemination and on days 5, 10 and 15 of gestation to determine plasma concentrations of homocysteine, methionine, THF, 5-methyl-THF, P5P, vitamin B12 and relative total folate-binding capacity. In occidental sows (YL and LD), the FA supplement tended to decrease uterine flush content of homocysteine (P=0·06) and concentrations of plasma homocysteine (P=0·09). Nulliparous YL sows had lower concentrations of plasma homocysteine, methionine, THF and 5-methyl-THF (P<0·05) than multiparous LD sows. Multiparous ML and LD sows had similar concentrations of plasma THF, 5-methyl-THF, methionine and vitamin B12, but ML sows had lower concentrations of plasma homocysteine (P<0·05). The vitamin B12 supplement increased concentrations of plasma vitamin B12 (P<0·05) both in multiparous ML and nulliparous YL sows, but had no effect on the composition of either uterine flush or plasma. The present results showed also that sows had a low vitamin B12 status (<200 pg/ml) and high circulating homocysteine levels (>15 μM) during the first 15 d of gestation. Furthermore, the vitamin B12 content in uterine secretions represented between 180 and 300 % of the total content in plasma. The low plasma concentrations of homocysteine in multiparous ML sows suggest a more efficient remethylation pathway which may not be dependent upon dietary supply of FA or vitamin B12. In nulliparous YL sows, low concentrations of both homocysteine and methionine suggest that the methionine requirement for protein deposition might have reduced the amount of methionine available for the methylation pathway. The results of the present experiment suggest that the reduction of uterine homocysteine may be an important aspect of the role of FA supplement on the uterine environment in occidental sows. The presence of high levels of vitamin B12 in uterine secretions merits further investigation in relation to embryonic development.

Keywords

FolatesHomocysteineGestationSow
Type
Research Article
Information
British Journal of Nutrition , Volume 88 , Issue 3 , September 2002 , pp. 253 - 263
Copyright
Copyright © The Nutrition Society 2002

References

Ambrosi, P, Rolland, PH, Bodard, H, Barlatier, A, Charpiot, P, Guisgand, G, Friggi, A, Ghiringhelli, O, Habib, G, Bouvenot, G, Garçon, D & Luccioni, R (1999) Effect of folate supplementation in hyperhomocysteinemic pigs. Journal of the American College of Cardiology 34, 274–279.Google Scholar
Antony, AC (1996) Folate receptors. Annual Review of Nutrition 16, 501–521.Google Scholar
Ashworth, CJ (1994) Nutritional factors related to embryonic mortality in the domestic species. In Embryonic Mortality in Domestic Species, pp. 179–194 [Zavy, MT and Geisert, RD, editors]. Boca Raton, FL: CRC Press Inc.Google Scholar
Barkow, B, Pietrzik, K & Flachowsky, G (2001) Effect of folic acid supplement on homocysteine in plasma of gestating sows. Archives of Animal Nutrition 54, 81–85.Google Scholar
Bässler, KH (1997) Enzymatic effects of folic acid and vitamin B12. International Journal of Vitamin Nutrition 67, 385–388.Google Scholar
Bilodeau, R, Matte, JJ, de Passillé, AMB, Girard, CL & Brisson, GJ (1989) Effects of floor type on serum folates, serum vitamin B12, plasma biotin and on growth performances of pigs. Canadian Journal of Animal Science 69, 779–788.Google Scholar
Canadian Council on Animal Care (1993) Guide to the Care and Use of Experimental Animals, vol. 1, Ottawa, Ont.: CCAC.Google Scholar
Chen, LH, Liu, ML, Hwang, HY, Chen, LS, Korenberg, J & Shane, B (1997) Human methionine synthase: cDNA cloning, gene localization, and expression. Journal of Biological Chemistry 272, 3628–3634.CrossRefGoogle ScholarPubMed
Czeizel, AE & Dudas, I (1992) Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. New England Journal of Medicine 327, 1832–1835.Google Scholar
Duquette, J, Matte, JJ, Farmer, C, Girard, CL & Laforest, JP (1997) Pre- and post-mating dietary supplements of folic acid and uterine secretory activity in gilts. Canadian Journal of Animal Science 77, 415–420.Google Scholar
Finkelstein, JD (1990) Methionine metabolism in mammals. Journal of Nutritional Biochemistry 1, 228–237.Google Scholar
Frederick, GL & Brisson, GJ (1961) Some observations on the relationship between vitamin B12 and reproduction in swine. Canadian Journal of Animal Science 41, 212–219.Google Scholar
Friedman, PA, Shia, MA & Wallace, JK (1977) A saturable high affinity binding site for transcobalamin II–vitamin B12 complexes in human placental membrane preparations. Journal of Clinical Investigation 59, 51–58.Google Scholar
Goyette, P, Summer, JS, Milos, R, Duncan, AM, Rosenblatt, DS, Matthews, R & Rozen, R (1994) Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification. Nature Genetics 7, 195–200.Google Scholar
Guay, F, Matte, JJ, Girard, CL, Palin, MF, Giguère, A & Laforest, JP (2002) Effect of genotype and parity, as well as folic acid and glycine supplement on embryonic development and folate metabolism during early pregnancy in pigs. Journal of Animal Science, (In the press).Google Scholar
Haley, CS & Lee, GJ (1993) Genetic basis of prolificacy in Meishan pigs. Journal of Reproduction and Fertility Supplement 48, 247–259.Google Scholar
Harmon, DL, Shields, DC, Woodside, JV, McMaster, D, Yarnell, JW, Young, IS, Peng, K, Shane, B, Evans, AE & Whitehead, AS (1999) Methionine synthase D919G polymorphism is significant but modest determinant of circulating homocysteine concentrations. Genetics Epidemiology 17, 298–309.Google Scholar
Jacques, PF, Bostom, AG, Williams, RR, Ellison, RC, Eckfeldt, JH, Rosenberg, IH, Selhub, J & Rozen, R (1996) Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 93, 7–9.Google Scholar
Jacques, PF, Selhub, J, Bostom, AG, Wilson, PWF & Rosenberg, IH (1999) The effect of folic acid fortification on plasma folate and total homocysteine concentrations. New England Journal of Medicine 340, 1449–1454.Google Scholar
Johansson, S, Dencker, L & Dantzer, V (2001) Immunohistochemical localization of retinoid binding proteins at the materno–fetal interface of the porcine epitheliochorial placenta. Biology of Reproduction 64, 60–68.Google Scholar
Johnson, RK (1981) Crossbreeding in swine: experimental results. Journal of Animal Science 52, 906–923.Google Scholar
Laforest, JP, King, GJ & Kennedy, TG (1992) Effect of topical application of oestradiol-17β and PGE2 on PGE-binding sites in porcine endometrium. Reproduction Nutrition and Development 32, 93–104.Google Scholar
Limpach, A, Dalton, M, Miles, R & Gadson, P (2000) Homocysteine inhibits retinoic acid synthesis: a mechanism for homocysteine-induced congenital defects. Experimental Cell Research 260, 166–174.Google Scholar
Lindemann, MD & Kornegay, ET (1989) Folic acid supplementation to diets of gestating–lactating swine over multiple parities. Journal of Animal Science 67, 459–464.Google Scholar
McNulty, H, McPartlin, JM, Weir, DG & Scott, JM (1995) Folate catabolism is related to growth rate in weaning rats. Journal of Nutrition 125, 99–103.Google Scholar
Malinow, MR, Kang, SS, Taylor, LM, Wong, PWK, Coull, B, Inahara, T, Mukerjee, D, Sexton, G & Upson, B (1989) Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusion disease. Circulation 79, 1180–1188.Google Scholar
Matte, JJ, Farmer, C, Girard, CL & Laforest, JP (1996) Dietary folic acid, uterine function and early embryonic development in sows. Canadian Journal of Animal Science 76, 427–433.Google Scholar
Matte, JJ & Girard, CL (1996) Changes of serum and blood volumes during gestation and lactation in multiparous sows. Canadian Journal of Animal Science 76, 263–266.Google Scholar
Matte, JJ, Girard, CL & Brisson, GJ (1984) Folic acid and reproductive performance of sows. Journal of Animal Science 59, 1020–1025.Google Scholar
Matte, JJ, Girard, CL & Tremblay, GF (1993) Effect of long-term addition of folic acid on folate status, growth performance, puberty attainment, and reproductive capacity of gilts. Journal of Animal Science 71, 151–157.Google Scholar
Matte, JJ, Ponter, AA & Sève, B (1997) Effects of chronic parenteral pyridoxine and acute enteric tryptophan on pyridoxine status, glycemia and insulinemia stimulated by enteric glucose in weanling piglets. Canadian Journal of Animal Science 77, 663–668.Google Scholar
Melnyk, S, Progribna, M, Progribny, I, Hine, RJ & James, SJ (1999) A new HPLC method for the stimultaneous determination of oxidized and reduced plasma aminothiols using coulometric electrochemical detection. Journal of Nutritional Biochemistry 10, 490–497.Google Scholar
Menezo, Y, Khatchadourian, C, Gharib, A, Hamidi, J, Greenland, T & Sarda, N (1989) Regulation of S-adenosyl methionine synthesis in mouse embryo. Life Sciences 44, 1601–1609.Google Scholar
Mills, JL, McPartlin, JM, Kirke, PN, Lee, YJ, Conley, MR, Weir, DG & Scott, JM (1995) Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet 345, 149–151.CrossRefGoogle ScholarPubMed
Nakagawa, H & Kimura, H (1968) Purification and properties of cystathionine synthetase from rat liver: separation of cystathionine synthetase from serine hydratase. Biochemical and Biophysical Research Communication 32, 208–212.Google Scholar
Natsuhori, M, Shimoda, M & Kokue, EI (1996) Alteration of plasma folates in gestating sows and newborn piglets. American Journal of Physiology 270, R99–R104.Google Scholar
Nelen, WLDM, Bulten, J, Steegers, EAP, Blom, HJ, Hanselaar, AGJM & Eskes, TKAB (2000) Maternal homocysteine and chorionic vascularization in recurrent early pregnancy loss. Human Reproduction 15, 954–960.Google Scholar
Pearson, PL, Klemcke, HG, Christenson, RK & Vallet, JL (1998) Porcine endometrial haptocorrin: cloning of partial cDNA and expression from days 10 to 40 of gestation. Biology of Reproduction 58, Suppl. 1, 193.Google Scholar
Perry, JS (1981) The mammalian fetal membranes. Journal of Reproduction and Fertility 62, 321–335.Google Scholar
Pope, WF & First, NL (1985) Factors affecting the survival of pig embryos. Theriogenology 23, 91–105.Google Scholar
Pusateri, AE, Rothschild, MF, Warner, CM & Ford, SF (1990) Changes in morphology, cell number, cell size and cellular estrogen content of individual littermate pig conceptuses on days 9 to 13 of gestation. Journal of Animal Science 68, 3727–3735.Google Scholar
Rivera, RM, Youngs, CR & Ford, SP (1996) A comparison of the number of inner cell mass and trophectoderm cells of preimplantation Meishan and Yorkshire pig embryos at similar developmental stages. Journal of Reproduction and Fertility 106, 111–116.Google Scholar
Rosenquist, TH, Ratashak, SA & Selhub, J (1996) Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid. Proceedings of National Academy of Sciences USA 93, 15227–15232.Google Scholar
Rosenquist, TH, Schneider, AM & Monaghan, DT (1999) N-Methyl-D-aspartate receptor agonist modulates homocysteine-induced developmental abnormalities. FASEB Journal 13, 1523–1531.Google Scholar
Schieffer, GW, Wheeler, GP & Cimino, CO (1984) Determination of folic acid in commercial diets by anion-exchange solid-phase extraction and subsequent reversed-phase high-performance liquid chromatography. Journal of Liquid Chromatography 7, 2659–2670.Google Scholar
Schwartz, SM, Siscovick, DS, Malinow, R, Rosendaal, FR, Beverly, RK, Hess, DL, Psaty, BM, Longstreth, WT, Koepsell, TD, Raghunathan, TE & Reitsman, PH (1997) Myocardial infarction in young women in relation to plasma total homocysteine, folate and a common variant in the methylenetetrahydrofolate reductase gene. Circulation 96, 412–417.Google Scholar
Scott, JM (1999) Folate and vitamin B12. Proceedings of the Nutrition Society 58, 441–448.Google Scholar
Scott, JM & Weir, DG (1981) The methyl folate trap. Lancet 15, 337–340.Google Scholar
Signer, EN, Dubrova, YE & Jeffreys, AJ (2000) Are DNA profiles breed-specific? A pilot study in pigs. Animal Genetics 31, 273–276.CrossRefGoogle ScholarPubMed
Smith, SM, Dickman, ED, Power, SC & Lancman, J (1998) Retinoids and their receptors in vertebrate embryogenesis. Journal of Nutrition 128, 467S–470S.CrossRefGoogle ScholarPubMed
Smolin, LA, Crenshaw, TD, Kurtycz, D & Benevenga, NJ (1983) Homocyst(e)ine accumulation in pigs fed diets deficient in vitamin B-6: relationship to atherosclerosis. Journal of Nutrition 113, 2122–2133.Google Scholar
Srivastava, SK & Beutler, E (1973) A new fluorometric method for the determination of pyridoxal 5 phosphate. Biochimica et Biophysica Acta 304, 765–773.Google Scholar
Steen, MT, Boddie, AM, Fisher, AJ, Macmahon, W, Saxe, D, Sullivan, KM, Dembure, PP & Elsas, LJ (1998) Neural-tube-defects are associated with low concentration of cobalamin (vitamin B12) in amniotic fluid. Prenatal Diagnosis 18, 545–555.Google Scholar
Tremblay, GF, Matte, JJ, Dufour, JJ & Brisson, GJ (1989) Survival rate and development of fetuses during the first 30 days of gestation after folic acid addition to a swine diet. Journal of Animal Science 67, 724–732.Google Scholar
Vallet, JL, Christenson, RK & Klemcke, HG (1999 a) Technical note: A radioimmunoassay for porcine intra-uterine folate binding protein. Journal of Animal Science 77, 1236–1240.CrossRefGoogle Scholar
Vallet, JL, Smith, TPL, Soustegard, T, Pearson, PL, Christenson, RK & Klemcke, HG (1999 b) Isolation of complementary deoxyribonucleic acids encoding putative secreted and membrane-bound folate binding proteins from endometrium of swine. Biology of Reproduction 61, 372–379.Google Scholar
VanAerts, LAGJM, Blom, HJ, Deabreu, RA, Trijbels, FJM, Eskes, TKAB, Peereboom-Stegeman, JHJC & Noordhoek, J (1994) Prevention of neural tube defects by and toxicity of L-homocysteine in cultured postimplantation rat embryos. Teratology 50, 348–360.Google Scholar
Whittemore, CT, Tullis, JB & Emmans, GC (1988) Protein growth in pigs. Animal Production 46, 437–445.Google Scholar
Wigertz, K & Jägerstad, M (1995) Comparison of HPLC and radioprotein-binding assay for determination of folates in milk and blood samples. Food Chemistry 54, 429–436.Google Scholar
Wilmut, I, Sales, DI & Ashworth, CJ (1985) The influence of variation in embryo stage and maternal hormone profiles on embryo survival in farm animals. Theriogenology 23, 107–119.Google Scholar
Wilson, ME & Ford, SP (1997) Differences in trophectoderm mitotic rate and P450 17α-hydroxylase expression between late preimplantation Meishan and Yorkshire conceptuses. Biology of Reproduction 56, 380–385.Google Scholar
Yen, HF, Isler, GA, Harvey, WR & Irvin, KM (1987) Factors affecting reproductive performance in swine. Journal of Animal Science 64, 1340–1348.Google Scholar
Yelich, JV, Pomp, D & Geisert, RD (1997) Detection of transcripts for retinoic acid receptors, retinal-binding protein, and transforming growth factors during rapid trophoblastic elongation in the porcine conceptus. Biology of Reproduction 57, 286–294.Google Scholar