Folic acid supplementation alleviates reduced ureteric branching, nephrogenesis, and global DNA methylation induced by maternal nutrient restriction in rat embryonic kidney
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...
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| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0230289 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0230289</identifier><identifier>PMID: 32251454</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Advertising executives ; Animals ; Aprotinin ; Binding sites ; Biology and life sciences ; Choline ; Dams ; Deoxyribonucleic acid ; Dietary supplements ; DNA ; DNA methylation ; DNMT1 protein ; Epigenetics ; Experiments ; Fetuses ; Folic acid ; Food ; Food availability ; Gene expression ; Hypertension ; Immunoglobulins ; Inhibition ; Kidneys ; Medical research ; Medicine and Health Sciences ; Methionine ; Methylation ; Methyltransferases ; Mimicry ; Nutrients ; Offspring ; Organ culture ; Pediatrics ; Physical Sciences ; Pregnancy ; Progeny ; Proteins ; Research and Analysis Methods ; Statistical analysis ; Supplementation ; Ureter ; Vitamin B</subject><ispartof>PloS one, 2020-04, Vol.15 (4), p.e0230289-e0230289</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Awazu, Hida. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Awazu, Hida 2020 Awazu, Hida</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-854279fca0103e43edba8192da6d6c1ce832d29b1523652d137e3418de8695313</citedby><cites>FETCH-LOGICAL-c758t-854279fca0103e43edba8192da6d6c1ce832d29b1523652d137e3418de8695313</cites><orcidid>0000-0001-9350-5339</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135271/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7135271/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32251454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Bader, Michael</contributor><creatorcontrib>Awazu, Midori</creatorcontrib><creatorcontrib>Hida, Mariko</creatorcontrib><title>Folic acid supplementation alleviates reduced ureteric branching, nephrogenesis, and global DNA methylation induced by maternal nutrient restriction in rat embryonic kidney</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>Advertising executives</subject><subject>Animals</subject><subject>Aprotinin</subject><subject>Binding sites</subject><subject>Biology and life sciences</subject><subject>Choline</subject><subject>Dams</subject><subject>Deoxyribonucleic acid</subject><subject>Dietary supplements</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNMT1 protein</subject><subject>Epigenetics</subject><subject>Experiments</subject><subject>Fetuses</subject><subject>Folic acid</subject><subject>Food</subject><subject>Food availability</subject><subject>Gene expression</subject><subject>Hypertension</subject><subject>Immunoglobulins</subject><subject>Inhibition</subject><subject>Kidneys</subject><subject>Medical research</subject><subject>Medicine and Health 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32251454</pmid><doi>10.1371/journal.pone.0230289</doi><tpages>e0230289</tpages><orcidid>https://orcid.org/0000-0001-9350-5339</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Advertising executives Animals Aprotinin Binding sites Biology and life sciences Choline Dams Deoxyribonucleic acid Dietary supplements DNA DNA methylation DNMT1 protein Epigenetics Experiments Fetuses Folic acid Food Food availability Gene expression Hypertension Immunoglobulins Inhibition Kidneys Medical research Medicine and Health Sciences Methionine Methylation Methyltransferases Mimicry Nutrients Offspring Organ culture Pediatrics Physical Sciences Pregnancy Progeny Proteins Research and Analysis Methods Statistical analysis Supplementation Ureter Vitamin B |
| title | Folic acid supplementation alleviates reduced ureteric branching, nephrogenesis, and global DNA methylation induced by maternal nutrient restriction in rat embryonic kidney |
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