Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of paternal folate deficiency on placental folate content and folate receptor ${\alpha}$ expression in rats

  • Kim, Hye-Won (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Choi, Yun-Jung (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Kim, Ki-Nam (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Tamura, Tsunenobu (Department of Nutritional Science and Food Management, Ewha Womans University) ;
  • Chang, Nam-Soo (Department of Nutritional Science and Food Management, Ewha Womans University)
  • Received : 2011.02.07
  • Accepted : 2011.04.05
  • Published : 2011.04.28
Download PDF
⟨ Previous Next ⟩

Abstract

We investigated the effect of paternal folate status on folate content and expression of the folate transporter folate receptor ${\alpha}$ ($FR{\alpha}$) in rat placental tissues. Rats were mated after males were fed a diet containing 0 mg of folic acid/kg of diet (paternal folate-deficient, PD) or 8 mg folic acid/kg of diet (paternal folate-supplemented, PS) for 4 weeks. At 20 days of gestation, the litter size, placental weight, and fetal weight were measured, and placental folate content (n=8/group) and expression of $FR{\alpha}$ (n=10/group) were analyzed by microbiological assay and Western blot analysis, respectively. Although there was no difference observed in litter size or fetal weight, but significant reduction (10%) in the weight of the placenta was observed in the PD group compared to that in the PS group. In the PD group, placental folate content was significantly lower (by 35%), whereas $FR{\alpha}$ expression was higher (by 130%) compared to the PS group. Our results suggest that paternal folate status plays a critical role in regulating placental folate metabolism and transport.

Keywords

References

  1. Belkacemi L, Nelson DM, Desai M, Ross MG. Maternal undernutrition influences placental-fetal development. Biol Reprod 2010;83:325-31. https://doi.org/10.1095/biolreprod.110.084517
  2. Wallace JM, Luther JS, Milne JS, Aitken RP, Redmer DA, Reynolds LP, Hay WW Jr. Nutritional modulation of adolescent pregnancy outcome - a review. Placenta 2006;27 Suppl A:S61-8.
  3. Tamura T, Picciano MF. Folate and human reproduction. Am J Clin Nutr 2006;83:993-1016.
  4. Henderson GI, Perez T, Schenker S, Mackins J, Antony AC. Maternal-to-fetal transfer of 5-methyltetrahydrofolate by the perfused human placental cotyledon: evidence for a concentrative role by placental folate receptors in fetal folate delivery. J Lab Clin Med 1995;126:184-203.
  5. Bisseling TM, Steegers EA, van den Heuvel JJ, Siero HL, van de Water FM, Walker AJ, Steegers-Theunissen RP, Smits P, Russel FG. Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction. Placenta 2004;25:588-93. https://doi.org/10.1016/j.placenta.2003.11.010
  6. Luhrs CA, Slomiany BL. A human membrane-associated folate binding protein is anchored by a glycosyl-phosphatidylinositol tail. J Biol Chem 1989;264:21446-9.
  7. Verma RS, Gullapalli S, Antony AC. Evidence that the hydrophobicity of isolated, in situ, and de novo-synthesized native human placental folate receptors is a function of glycosylphosphatidylinositol anchoring to membranes. J Biol Chem 1992;267:4119-27.
  8. Matherly LH, Goldman DI. Membrane transport of folates. Vitam Horm 2003;66:403-56.
  9. Baker H, Frank O, Deangelis B, Feingold S, Kaminetzky HA. Role of placenta in maternal-fetal vitamin transfer in humans. Am J Obstet Gynecol 1981;141:792-6.
  10. Solanky N, Requena Jimenez A, D'Souza SW, Sibley CP, Glazier JD. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta 2010;31:134-43. https://doi.org/10.1016/j.placenta.2009.11.017
  11. Kim JM, Hong K, Lee JH, Lee S, Chang N. Effect of folate deficiency on placental DNA methylation in hyperhomocysteinemic rats. J Nutr Biochem 2009;20:172-6. https://doi.org/10.1016/j.jnutbio.2008.01.010
  12. Ray JG, Laskin CA. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review. Placenta 1999;20:519-29. https://doi.org/10.1053/plac.1999.0417
  13. Fowden AL, Coan PM, Angiolini E, Burton GJ, Constancia M. Imprinted genes and the epigenetic regulation of placental phenotype. Prog Biophys Mol Biol 2010 Nov 23. [Epub ahead of print].
  14. Wallock LM, Tamura T, Mayr CA, Johnston KE, Ames BN, Jacob RA. Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers. Fertil Steril 2001;75:252-9. https://doi.org/10.1016/S0015-0282(00)01697-6
  15. Young SS, Eskenazi B, Marchetti FM, Block G, Wyrobek AJ. The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men. Hum Reprod 2008;23:1014-22. https://doi.org/10.1093/humrep/den036
  16. Boxmeer JC, Smit M, Utomo E, Romijn JC, Eijkemans MJ, Lindemans J, Laven JS, Macklon NS, Steegers EA, Steegers-Theunissen RP. Low folate in seminal plasma is associated with increased sperm DNA damage. Fertil Steril 2009;92:548-56. https://doi.org/10.1016/j.fertnstert.2008.06.010
  17. Kim HW, Lee YA, Kim HH, Lee S, Chang N. Paternal folate deficiency during reproduction influences folate concentrations in the brain of the offspring. FASEB J 2010;24:915.7.
  18. Tamura T. Microbiological assay of folates. Folic Acid Metabolism in Health and Disease. Picciano MF, Stokstad ELR, Gregory JF III, editors. New York: Wiley-Liss; 1990. p.121-37.
  19. Mooij PN, Thomas CM, Doesburg WH, Eskes TK. The effects of periconceptional folic acid and vitamin supplementation on maternal folate levels and on neurulating hamster embryos in vivo. Int J Vitam Nutr Res 1993;63:212-6.
  20. Tamura T, Goldenberg RL, Freeberg LE, Cliver SP, Cutter GR, Hoffman HJ. Maternal serum folate and zinc concentrations and their relationships to pregnancy outcome. Am J Clin Nutr 1992;56:365-70.
  21. Timmermans S, Jaddoe VW, Hofman A, Steegers-Theunissen RP, Steegers EA. Periconception folic acid supplementation, fetal growth and the risks of low birth weight and preterm birth: the Generation R Study. Br J Nutr 2009;102:777-85. https://doi.org/10.1017/S0007114509288994
  22. Lindzon G, O'Connor DL. Folate during reproduction: the Canadian experience with folic acid for fortification. Nutr Res Pract 2007;1:163-74. https://doi.org/10.4162/nrp.2007.1.3.163
  23. van Eijsden M, Smits LJ, van der Wal MF, Bonsel GJ. Association between short interpregnancy intervals and term birth weight: the role of folate depletion. Am J Clin Nutr 2008;88:147-53.
  24. Xiao S, Hansen DK, Horsley ET, Tang YS, Khan RA, Stabler SP, Jayaram HN, Antony AC. Maternal folate deficiency results in selective upregulation of folate receptors and heterogeneous nuclear ribonucleoprotein-E1 associated with multiple subtle aberrations in fetal tissues. Birth Defects Res A Clin Mol Teratol 2005;73:6-28. https://doi.org/10.1002/bdra.20105
  25. Engeham SF, Haase A, Langley-Evans SC. Supplementation of a maternal low-protein diet in rat pregnancy with folic acid ameliorates programming effects upon feeding behaviour in the absence of disturbances to the methionine-homocysteine cycle. Br J Nutr 2010;103:996-1007. https://doi.org/10.1017/S0007114509992662
  26. Chan D, Cushnie DW, Neaga OR, Lawrance AK, Rozen R, Trasler JM. Strain-specific defects in testicular development and sperm epigenetic patterns in 5,10-methylenetetrahydrofolate reductase-deficient mice. Endocrinology 2010;151:3363-73. https://doi.org/10.1210/en.2009-1340
  27. Dhillon VS, Shahid M, Husain SA. Associations of MTHFR DNMT3b 4977 bp deletion in mtDNA and GSTM1 deletion, and aberrant CpG island hypermethylation of GSTM1 in nonobstructive infertility in Indian men. Mol Hum Reprod 2007;13:213-22. https://doi.org/10.1093/molehr/gal118
  28. Park BH, Kim YJ, Park JS, Lee HY, Ha EH, Min JW, Park HS. Folate and homocysteine levels during pregnancy affect DNA methylation in human placenta. J Prev Med Public Health 2005;38:437-42.
  29. Jenkins TG, Carrell DT. The paternal epigenome and embryogenesis: poising mechanisms for development. Asian J Androl 2011;13:76-80. https://doi.org/10.1038/aja.2010.61
  30. Nafee TM, Farrell WE, Carroll WD, Fryer AA, Ismail KMK. Epigenetic control of fetal gene expression. BJOG 2008;115:158-68.

Cited by

  1. Effects of paternal folate deficiency on the expression of insulin-like growth factor-2 and global DNA methylation in the fetal brain vol.57, pp.4, 2012, https://doi.org/10.1002/mnfr.201200558
  2. Effects of parental folate deficiency on the folate content, global DNA methylation, and expressions of FRα, IGF-2 and IGF-1R in the postnatal rat liver vol.7, pp.4, 2013, https://doi.org/10.4162/nrp.2013.7.4.281
  3. Folate Receptor Alpha, Mesothelin and Megakaryocyte Potentiating Factor as Potential Serum Markers of Chronic Kidney Disease vol.9, pp.1177-2719, 2014, https://doi.org/10.4137/BMI.S15245
  4. Folic Acid Supplementation during Pregnancy Induces Sex-Specific Changes in Methylation and Expression of Placental 11β-Hydroxysteroid Dehydrogenase 2 in Rats vol.10, pp.3, 2015, https://doi.org/10.1371/journal.pone.0121098
  5. Folate Transporters in Placentas from Preterm Newborns and Their Relation to Cord Blood Folate and Vitamin B12 Levels vol.12, pp.1, 2017, https://doi.org/10.1371/journal.pone.0170389
  6. Mechanisms of transgenerational inheritance of addictive-like behaviors vol.264, pp.None, 2011, https://doi.org/10.1016/j.neuroscience.2013.07.064
  7. Should Men Take Prenatal Vitamins? vol.3, pp.3, 2014, https://doi.org/10.4172/2161-038x.1000139
  8. Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube Defects in the Fetus: Evidence from Case-Control and Family-Based Triad Approaches : SHMT1 and NTD Susceptibility in t vol.109, pp.13, 2011, https://doi.org/10.1002/bdr2.23623
  9. Paternal Folate Status and Sperm Quality, Pregnancy Outcomes, and Epigenetics: A Systematic Review and Meta‐Analysis vol.64, pp.9, 2011, https://doi.org/10.1002/mnfr.201900696
  10. Consequences of Paternal Nutrition on Offspring Health and Disease vol.13, pp.8, 2021, https://doi.org/10.3390/nu13082818