{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:11Z","timestamp":1783570991587,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,28]],"date-time":"2021-08-28T00:00:00Z","timestamp":1630108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Department of Agriculture","award":["USDA-AFRI-NIFA 2013-01919"],"award-info":[{"award-number":["USDA-AFRI-NIFA 2013-01919"]}]},{"name":"U.S. Department of Agriculture","award":["USDA-AFRI-NIFA 2014-01982"],"award-info":[{"award-number":["USDA-AFRI-NIFA 2014-01982"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>The mechanisms by which fetal programming predisposes offspring to reduced \u03b2-cell function later in life are poorly understood. We hypothesized that maternal under- and over-nutrition during gestation would negatively affect offspring pancreas development and alter DNA methylation patterns. Pregnant ewes (n = 78) were fed 100, 60, or 140% of NRC requirements beginning at d 30.2 \u00b1 0.2 of gestation. The fetuses are referred to as CON, RES, and OVER, respectively. Fetal pancreas tissue was collected at d 90 or 135 of gestation or within 24 h of birth. Tissue was preserved for histological (n = 8 to 9 offspring per treatment per time point) and DNA methylation analyses (n = 3 to 4 fetuses per treatment per sex). At d 135, OVER exhibited an increased islet size, reduced islet number, and greater insulin positive area compared with CON (p \u2264 0.03). An increased islet size was also observed at d 135 in RES (p \u2264 0.03) compared with CON. Cellular proliferation was reduced at birth in OVER vs. CON (p = 0.01). In the RES vs. CON females, 62% of the differentially methylated regions (DMRs) were hypomethylated (p \u2264 0.001). In the RES vs. CON males, 93% of the DMRs were hypermethylated (p \u2264 0.001). In OVER, 66 and 80% of the DMRs were hypermethylated in the female and male offspring compared with CON (p \u2264 0.001). In conclusion, changes to maternal diet during pregnancy affects the islet hypertrophy and cellular proliferation of the offspring at early post-natal time points. Additionally, changes in DNA methylation patterns appear to be in a diet-specific and sex-dependent manner.<\/jats:p>","DOI":"10.3390\/ani11092531","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T21:45:16Z","timestamp":1630273516000},"page":"2531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Maternal Under- and Over-Nutrition during Gestation Causes Islet Hypertrophy and Sex-Specific Changes to Pancreas DNA Methylation in Fetal Sheep"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria","family":"Peterson","sequence":"first","affiliation":[{"name":"Department of Fisheries, Animal and Veterinary Science, University of Rhode Island, Kingston, RI 02891, USA"},{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Gauvin","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sambhu","family":"Pillai","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn","family":"McFadden","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelynn","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Zinn","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Govoni","sequence":"additional","affiliation":[{"name":"Department of Animal Science, University of Connecticut, Storrs, CT 06289, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/MPA.0b013e31802ee9ae","article-title":"Compromised-Cell Development and Cell Dysfunction in Weanling Offspring from Dams Maintained on a High-Fat Diet during Gestation","volume":"34","author":"Cerf","year":"2007","journal-title":"Pancreas"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ydbio.2008.10.024","article-title":"Developmental biology of the pancreas: A comprehensive review","volume":"326","author":"Gittes","year":"2009","journal-title":"Dev. 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