{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:12:03Z","timestamp":1788246723213,"version":"build-2803163510"},"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["Scholarship 2014\/50938-8"],"award-info":[{"award-number":["Scholarship 2014\/50938-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/12486-5"],"award-info":[{"award-number":["2013\/12486-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["465699\/2014-6"],"award-info":[{"award-number":["465699\/2014-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Here, we have demonstrated that gestational low-protein (LP) intake offspring present lower birth weight, reduced nephron numbers, renal salt excretion, arterial hypertension, and renal failure development compared to regular protein (NP) intake rats in adulthood. We evaluated the expression of various miRNAs and predicted target genes in the kidney in gestational 17-days LP (DG-17) fetal metanephros to identify molecular pathways involved in the proliferation and differentiation of renal embryonic or fetal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Pregnant Wistar rats were classified into two groups based on protein supply during pregnancy: NP (regular protein diet, 17%) or LP diet (6%).\n                      <jats:italic>Renal miRNA sequencing (miRNA-Seq)<\/jats:italic>\n                      performed on the MiSeq platform,\n                      <jats:italic>RT-qPCR of predicted target genes<\/jats:italic>\n                      , immunohistochemistry, and morphological analysis of 17-DG NP and LP offspring were performed using previously described methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 44 miRNAs, of which 19 were up and 25 downregulated, were identified in 17-DG LP fetuses compared to age-matched NP offspring. We selected 7 miRNAs involved in proliferation, differentiation, and cellular apoptosis. Our findings revealed reduced cell number and Six-2 and c-Myc immunoreactivity in metanephros cap (CM) and ureter bud (UB) in 17-DG LP fetuses. Ki-67 immunoreactivity in CM was 48% lesser in LP compared to age-matched NP fetuses. Conversely, in LP CM and UB, \u03b2-catenin was 154%, and 85% increased, respectively. Furthermore, mTOR immunoreactivity was higher in LP CM (139%) and UB (104%) compared to that in NP offspring. TGF\u03b2-1 positive cells in the UB increased by approximately 30% in the LP offspring. Moreover, ZEB1 metanephros-stained cells increased by 30% in the LP offspring. ZEB2 immunofluorescence, although present in the entire metanephros, was similar in both experimental groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Maternal protein restriction changes the expression of miRNAs, mRNAs, and proteins involved in proliferation, differentiation, and apoptosis during renal development. Renal ontogenic dysfunction, caused by maternal protein restriction, promotes reduced reciprocal interaction between CM and UB; consequently, a programmed and expressive decrease in nephron number occurs in the fetus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0246289","type":"journal-article","created":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T18:51:42Z","timestamp":1612723902000},"page":"e0246289","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["Impact of gestational low-protein intake on embryonic kidney microRNA expression and in nephron progenitor cells of the male fetus"],"prefix":"10.1371","volume":"16","author":[{"given":"Let\u00edcia de Barros","family":"Sene","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wellerson Rodrigo","family":"Scarano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Zapparoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-385X","authenticated-orcid":true,"given":"Jos\u00e9 Ant\u00f4nio Rocha","family":"Gontijo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patr\u00edcia Aline","family":"Boer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"pone.0246289.ref001","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1079\/PNS2005478","article-title":"Developmental programming of health and disease","volume":"65","author":"SC Langley-Evans","year":"2006","journal-title":"Proc Nutr Soc"},{"key":"pone.0246289.ref002","first-page":"401S","article-title":"Symposium: The Effects of Childhood Diet on Adult Health and Disease Psychological Influences on Childhood Diet 1","volume":"128","author":"A Lucas","year":"1998","journal-title":"J Nutr"},{"key":"pone.0246289.ref003","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1093\/ndt\/gfp505","article-title":"Expression of renin-angiotensin system signaling compounds in maternal protein-restricted rats: effect on renal sodium excretion and blood pressure","volume":"25","author":"FF Mesquita","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"pone.0246289.ref004","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1590\/S0100-879X2010007500113","article-title":"Maternal undernutrition and the offspring kidney: From fetal to adult life","volume":"43","author":"FF Mesquita","year":"2010","journal-title":"Braz J Med Biol Res"},{"key":"pone.0246289.ref005","doi-asserted-by":"crossref","first-page":"e71310","DOI":"10.1371\/journal.pone.0071310","article-title":"Involvement of renal corpuscle microRNA expression on epithelial-to-mesenchymal transition in maternal low protein diet in adult programmed rats","volume":"19","author":"LB Sene","year":"2013","journal-title":"PLoS One"},{"key":"pone.0246289.ref006","first-page":"221","article-title":"Gestational low-protein intake enhances whole-kidney miR-192 and miR-200 family expression and epithelial-to-mesenchymal transition in rat adult male offspring","volume":"22","author":"LB Sene","year":"2018","journal-title":"J Exp Biol"},{"key":"pone.0246289.ref007","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1159\/000094538","article-title":"Consequences of intrauterine growth restriction for the kidney","volume":"29","author":"M Schreuder","year":"2006","journal-title":"Kidney Blood Press Res"},{"key":"pone.0246289.ref008","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/jez.1401300207","article-title":"Inductive interaction in the development of the mouse metanephros","volume":"130","author":"C Grobstein","year":"1955","journal-title":"J. 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