{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:47:25Z","timestamp":1791010045378,"version":"4.1.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The impact of obesity on pregnancy outcomes and offspring health has received increasing attention. Semaglutide have been shown to have significant effects on weight management. This study aims to evaluate whether Pre-pregnancy Semaglutide Intervention (PpSI) improves maternal metabolic disorders before and during pregnancy, affects placental function and fetal hypothalamic neuropeptide expression during late-gestation and its underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, female SD rats were divided into three groups: control diet (CHOW), high-fat diet (HFD), and high-fat diet with PpSI. After mating with males, maternal metabolic outcomes, placental morphology, nutrient transport, and fetal hypothalamic gene expression were assessed on gestational Day 20.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PpSI significantly reduced pre-pregnancy weight gain and gestational weight gain of the dams compared with the HFD group. It also reduced maternal blood lipid levels before and during pregnancy. In male placentas of HFD group, the thickness of the labyrinth was decreased, the mRNA expression of amino acid transporters was upregulated, and the phosphorylation of STAT3 and ERK1\/2 was increased, while PpSI normalized these changes. In male fetuses, maternal HFD decreased plasma leptin levels, reduced hypothalamic STAT3 signaling and appetite-related gene expression, while pre-pregnancy semaglutide intervention improved these changes. Compared with males, maternal HFD had less effect on placenta or fetal hypothalamic leptin signaling in females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PpSI improves maternal lipid metabolism before and during pregnancy, and improves placental nutritional transport and fetal hypothalamic appetite-related gene expression, which provides a potential strategy for pre-pregnancy intervention in obese women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/biolre\/ioaf178","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T11:34:57Z","timestamp":1754393697000},"page":"1463-1474","source":"Crossref","is-referenced-by-count":8,"title":["Pre-pregnancy treatment of semaglutide improves high-fat-diet-induced placental and fetal hypothalamic alterations in a sex-specific manner in rats"],"prefix":"10.1093","volume":"113","author":[{"given":"Jingyue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]},{"name":"Institute of Neuroscience, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Second Affiliated Hospital of Xi\u2019an Jiaotong University , Xi\u2019an, Shaanxi ,","place":["China"]},{"name":"Postdoctoral Research Station, School of Nursing, Health Science Center, Xi'an Jiaotong University , Xi'an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Second Department of Geriatrics, The First Affiliated Hospital of Xi\u2019an Jiaotong University , Xi'an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Niu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , Xi'an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]},{"name":"Institute of Neuroscience, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyan","family":"Pan","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , Xi'an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxi","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , Xi'an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duowen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]},{"name":"Institute of Neuroscience, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9500-8387","authenticated-orcid":false,"given":"Lin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]},{"name":"Institute of Neuroscience, Translational Medicine Institute, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-0579","authenticated-orcid":false,"given":"Bo","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University Health Science Center , Xi\u2019an, Shaanxi ,","place":["China"]},{"name":"Institute of Neuroscience, 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