{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:21:58Z","timestamp":1791476518648,"version":"4.3.4"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gestational diabetes mellitus (GDM) has been linked to altered leptin (LEP) gene methylation, which may disrupt maternal glucose metabolism and the associated placental signaling. However, the changes of LEP methylation involved in GDM pathophysiology throughout pregnancy remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Female C57BL\/6J mice (6\u20138\u00a0weeks old) were randomly divided into control and GDM groups (n = 40 each). The GDM group was fed a high-fat diet for 4\u00a0weeks before mating and given a single streptozotocin injection (120\u00a0mg\/kg, intraperitoneal injection) on gestational day 2, while controls received standard chow and citrate buffer. Fasting blood glucose and body weight were recorded at baseline, gestational days 5, 12, and 18, and postpartum day 1. Oral glucose tolerance tests (OGTTs) were performed at corresponding stages. Blood was collected for measurement of serum leptin concentrations by ELISA. Leptin protein expression and LEP promoter methylation in decidual tissues were analyzed by Western blot and bisulfite pyrosequencing, respectively. Weighted least-squares regression was used to evaluate the associations between leptin, LEP promoter methylation, and glucose metabolism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The high-fat diet and streptozotocin (HFD + STZ) combination successfully induced a GDM phenotype, as evidenced by early and persistent hyperglycemia and impaired glucose tolerance. Serum leptin levels were significantly increased in GDM mice before pregnancy and returned to the levels of pre-pregnancy in postpartum, indicating that the decidua plays an important role in the dynamic regulation of leptin during pregnancy. Western blot analysis confirmed higher leptin expression in the decidual tissue of GDM mice, while bisulfite pyrosequencing revealed significant demethylation of the LEP promoter. WLS analysis showed that leptin upregulation in GDM was closely associated with epigenetic remodeling at specific CpG sites within the LEP promoter, whereas the relationship between promoter demethylation and FBG was altered in GDM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Decidual LEP promoter demethylation is associated with hyperleptinemia and shows an epigenetic mechanism linking GDM. LEP promoter demethylation may reflect the metabolic disturbance in GDM and serve as a potential early marker for GDM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1729477","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:41:55Z","timestamp":1768977715000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Demethylation of leptin promoter in gestational diabetes mellitus: evidence from a mouse model"],"prefix":"10.3389","volume":"14","author":[{"given":"Linlin","family":"Hu","sequence":"first","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]},{"name":"Department of obstetrics, The Second Affiliated Hospital of Fujian Medical University","place":["Quanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihuang","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Tu","sequence":"additional","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]},{"name":"Nan\u2019an Maternal and Child Health Hospital","place":["Quanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shupei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Fujian Maternity and Child Health Hospital","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Huang","sequence":"additional","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Lin","sequence":"additional","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Ji","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Macau, Taipa","place":["Taipa, Macao SAR, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yi","sequence":"additional","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]},{"name":"Department of Gynecologic Oncology, Fujian Maternity and Child Health Hospital","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangqin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Fujian Medical University","place":["Fuzhou, China"]},{"name":"Department of Gynecologic Oncology, Fujian Maternity and Child Health Hospital","place":["Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1186\/s12944-019-1169-2","article-title":"Leptin, resistin and visfatin as useful predictors of gestational diabetes mellitus","volume":"18","author":"Bawah","year":"2019","journal-title":"Lipids Health Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s11892-019-1267-6","article-title":"Hyperglycemia during pregnancy and long-term offspring outcomes","volume":"19","author":"Bianco","year":"2019","journal-title":"Curr. 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