{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:24:34Z","timestamp":1760059474899,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u00e3o Paulo Research Foundation (FAPESP)","award":["13\/16922-4"],"award-info":[{"award-number":["13\/16922-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Hyperglycemia during fetal development disturbs extracellular matrix (ECM) synthesis and deposition patterns, which disrupts organogenesis and adult organ function. Although the ECM cooperates in pancreas development, little is known about the effects of hyperglycemia on the pancreatic ECM during development. This study investigates the effect of severe maternal hyperglycemia on ECM composition and endocrine pancreas development in E19.0 mouse fetuses. Deposition patterns of pan-laminin, laminin (alpha 1 and gamma 1 chains) and integrin alpha 3 were evaluated by immunostaining. The proliferative index of islet cells and alpha and beta cell distribution were evaluated by PCNA, glucagon and insulin immunostaining, respectively. Pdx1 and Pax4 expressions were analyzed by RT-qPCR. While for pan-laminin and laminin (alpha1 and gamma1 chains) deposition was weaker in the endocrine pancreas of hyperglycemic mothers\u2019 fetuses, integrin alpha 3 deposition in the basement membrane was increased. The proliferative index of endocrine cells was lower in the hyperglycemic group, while the beta-cell area was increased. In addition, there was a tendency towards lower Pdx1 and increased Pdx4 expression. These data suggest that maternal hyperglycemia alters fetal endocrine pancreas morphogenesis by modifying peri-islet basement membrane molecule patterns, promoting a decrease in endocrine cell proliferation associated with changes in the expression of important growth factors for the beta cells differentiated and the proliferative state.<\/jats:p>","DOI":"10.3390\/biology14060728","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T08:43:58Z","timestamp":1750322638000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Maternal Hyperglycemia on Fetal Pancreatic Islet Development"],"prefix":"10.3390","volume":"14","author":[{"given":"Carina Pereira","family":"Dias","sequence":"first","affiliation":[{"name":"Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel Raony","family":"Teixeira Paiva de Moraes","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda Angela","family":"Correia Barrence","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila Stephanie","family":"Balbino da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4577-6393","authenticated-orcid":false,"given":"Basilio","family":"Smuckzec","sequence":"additional","affiliation":[{"name":"Tumor Biology Laboratory, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda","family":"Ortis","sequence":"additional","affiliation":[{"name":"Molecular Mechanism of Beta Cell Death Laboratory, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Telma Maria Ten\u00f3rio","family":"Zorn","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive and Extracellular Matrix Biology, Department of Cell and Developmental Biology, Institute of Biomedical Sciences, Cidade Universit\u00e1ria, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1677\/joe.0.0730339","article-title":"Rat fetal endocrine pancreas in experimental diabetes","volume":"73","author":"Aerts","year":"1977","journal-title":"J. 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