Folic Acid Supplementation Alleviates Reduced Ureteric Branching, Nephrogenesis, and Global DNA Methylation Induced by Maternal Nutrient Restriction in Rat Embryonic Kidney

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2020 Apr 7

PMID 32251454

Citations 7

Authors

Midori Awazu

Mariko Hida

Affiliations

Soon will be listed here.

Abstract

We previously reported that maternal nutrient restriction (NR) inhibited ureteric branching, metanephric growth, and nephrogenesis in the rat. Here we examined whether folic acid, a methyl-group donor, rescues the inhibition of kidney development induced by NR and whether DNA methylation is involved in it. The offspring of dams given food ad libitum (CON) and those subjected to 50% food restriction (NR) were examined. NR significantly reduced ureteric tip number at embryonic day 14, which was attenuated by folic acid supplementation to nutrient restricted dams. At embryonic day 18, glomerular number, kidney weight, and global DNA methylation were reduced by NR, and maternal folic acid supplementation again alleviated them. Among DNA methyltransferases (DNMTs), DNMT1 was strongly expressed at embryonic day 15 in CON but was reduced in NR. In organ culture, an inhibitor of DNA methylation 5-aza-2 '-deoxycytidine as well as medium lacking methyl donors folic acid, choline, and methionine, significantly decreased ureteric tip number and kidney size mimicking the effect of NR. In conclusion, global DNA methylation is necessary for normal kidney development. Folic acid supplementation to nutrient restricted dams alleviated the impaired kidney development and DNA methylation in the offspring.

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References

Sebinger D, Unbekandt M, Ganeva V, Ofenbauer A, Werner C, Davies J . A novel, low-volume method for organ culture of embryonic kidneys that allows development of cortico-medullary anatomical organization. PLoS One. 2010; 5(5):e10550. PMC: 2866658. DOI: 10.1371/journal.pone.0010550. View

Unterberger A, Szyf M, Nathanielsz P, Cox L . Organ and gestational age effects of maternal nutrient restriction on global methylation in fetal baboons. J Med Primatol. 2009; 38(4):219-27. PMC: 2872243. DOI: 10.1111/j.1600-0684.2008.00320.x. View

Xie R, Liu Y, Retnakaran R, MacFarlane A, Hamilton J, Smith G . Maternal folate status and obesity/insulin resistance in the offspring: a systematic review. Int J Obes (Lond). 2015; 40(1):1-9. DOI: 10.1038/ijo.2015.189. View

Gupta I, Lapointe M, Yu O . Morphogenesis during mouse embryonic kidney explant culture. Kidney Int. 2002; 63(1):365-76. DOI: 10.1046/j.1523-1755.2003.00715.x. View

Langley-Evans S, Welham S, Jackson A . Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci. 1999; 64(11):965-74. DOI: 10.1016/s0024-3205(99)00022-3. View

Tian Y, Luo N, Chen N, Lun Y, Gu X, Li Z . Maternal nicotinamide supplementation causes global DNA hypomethylation, uracil hypo-incorporation and gene expression changes in fetal rats. Br J Nutr. 2014; 111(9):1594-601. DOI: 10.1017/S0007114513004054. View

Pham T, MacLennan N, Chiu C, Laksana G, Hsu J, Lane R . Uteroplacental insufficiency increases apoptosis and alters p53 gene methylation in the full-term IUGR rat kidney. Am J Physiol Regul Integr Comp Physiol. 2003; 285(5):R962-70. DOI: 10.1152/ajpregu.00201.2003. View

Awazu M, Hida M . Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats. Pediatr Res. 2015; 77(5):633-9. DOI: 10.1038/pr.2015.24. View

Zhang N . Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. Anim Nutr. 2018; 1(3):144-151. PMC: 5945948. DOI: 10.1016/j.aninu.2015.09.002. View

10.

Lee H . Impact of Maternal Diet on the Epigenome during In Utero Life and the Developmental Programming of Diseases in Childhood and Adulthood. Nutrients. 2015; 7(11):9492-507. PMC: 4663595. DOI: 10.3390/nu7115467. View

11.

Hu L, Liu Y, Yan C, Peng X, Xu Q, Xuan Y . Postnatal nutritional restriction affects growth and immune function of piglets with intra-uterine growth restriction. Br J Nutr. 2015; 114(1):53-62. DOI: 10.1017/S0007114515001579. View

12.

Mitchell C, Schneper L, Notterman D . DNA methylation, early life environment, and health outcomes. Pediatr Res. 2015; 79(1-2):212-9. PMC: 4798238. DOI: 10.1038/pr.2015.193. View

13.

Torrens C, Brawley L, Anthony F, Dance C, Dunn R, Jackson A . Folate supplementation during pregnancy improves offspring cardiovascular dysfunction induced by protein restriction. Hypertension. 2006; 47(5):982-7. DOI: 10.1161/01.HYP.0000215580.43711.d1. View

14.

MacLennan N, James S, Melnyk S, Piroozi A, Jernigan S, Hsu J . Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats. Physiol Genomics. 2004; 18(1):43-50. DOI: 10.1152/physiolgenomics.00042.2004. View

15.

Duthie S . Folic acid deficiency and cancer: mechanisms of DNA instability. Br Med Bull. 2000; 55(3):578-92. DOI: 10.1258/0007142991902646. View

16.

Gopalakrishnan G, Gardner D, Dandrea J, Langley-Evans S, Pearce S, Kurlak L . Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep. Br J Nutr. 2005; 94(6):938-47. PMC: 2656281. DOI: 10.1079/bjn20051559. View

17.

Liu J, Chen D, Yu B, Mao X . Effect of maternal folic acid supplementation on hepatic one-carbon unit associated gene expressions in newborn piglets. Mol Biol Rep. 2010; 38(6):3849-56. DOI: 10.1007/s11033-010-0500-9. View

18.

Li E, Bestor T, Jaenisch R . Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992; 69(6):915-26. DOI: 10.1016/0092-8674(92)90611-f. View

19.

Welham S, Wade A, Woolf A . Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int. 2002; 61(4):1231-42. DOI: 10.1046/j.1523-1755.2002.00264.x. View

20.

Li S, Park J, Guan Y, Chung K, Shrestha R, Palmer M . DNMT1 in Progenitor Cells Is Essential for Transposable Element Silencing and Kidney Development. J Am Soc Nephrol. 2019; 30(4):594-609. PMC: 6442333. DOI: 10.1681/ASN.2018070687. View