{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:19:19Z","timestamp":1790605159468,"version":"4.1.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Ministry of Education, Korea","award":["F22YY8109033"],"award-info":[{"award-number":["F22YY8109033"]}]},{"name":"Biomedical Research Institute","award":["20210020"],"award-info":[{"award-number":["20210020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.<\/jats:p>","DOI":"10.1093\/biolre\/ioad059","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T13:03:28Z","timestamp":1685538208000},"page":"215-226","source":"Crossref","is-referenced-by-count":7,"title":["Regulation of uterus and placenta remodeling under high estradiol levels in gestational diabetes mellitus models"],"prefix":"10.1093","volume":"109","author":[{"given":"Da Hee","family":"Kang","sequence":"first","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jae","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"},{"name":"Korea Institute of Toxicology Developmental and Reproductive Toxicology Research Group, , Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsayed A","family":"Mohamed","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"},{"name":"Assiut University Department of Genetics, , Assiut, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Som","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jea Sic","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon-Gu","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geun-Shik","family":"Lee","sequence":"additional","affiliation":[{"name":"Kangwon National University Department of Veterinary Medicine, , Chuncheon, Gangwon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Ju","family":"Hong","sequence":"additional","affiliation":[{"name":"Chungnam National University Department of Veterinary Medicine, , Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhwan","family":"Ahn","sequence":"additional","affiliation":[{"name":"Jeju National University Department of Veterinary Medicine, , Jeju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eui-Man","family":"Jung","sequence":"additional","affiliation":[{"name":"Pusan National University Department of Molecular Biology, College of Natural Sciences, , Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beum-Soo","family":"An","sequence":"additional","affiliation":[{"name":"College of Natural Resources & Life Science, Pusan National University Department of Biomaterials Science (BK21 Four Program), , Miryang, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Chul","family":"Kim","sequence":"additional","affiliation":[{"name":"Pusan National University School of Medicine Department of Obstetrics and Gynecology, , Busan, Republic of Korea"},{"name":"Pusan National University Hospital Biomedical Research Institute, , Busan, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"2023081606480771400_ref1","doi-asserted-by":"crossref","first-page":"331","DOI":"10.4183\/aeb.2016.331","article-title":"Gestational diabetes. 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