{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:56:35Z","timestamp":1767869795872,"version":"3.49.0"},"reference-count":159,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Over a quarter of human pregnancies are associated with complications, including fetal growth restriction, pre-eclampsia and gestational diabetes. These are major causes of maternal and fetal morbidity and mortality, and also lead to a 3\u20135-fold increased risk of subsequent development of cardio-metabolic diseases. Although the mechanistic details remain elusive, a dysfunctional placenta is central to the pathophysiology of these conditions. The placenta ensures sufficient nutrient supply to the fetus without compromising maternal wellbeing. This balance is achieved by the secretion of large quantities of placental-derived peptide hormones into the maternal circulation. Consequently, the placenta is susceptible to endoplasmic reticulum (ER) stress, and we were the first to demonstrate the presence of ER stress in placentas from complicated pregnancies. The mouse placenta provides an ideal model for studying the impact of ER stress as it is composed of two distinct regions, an endocrine zone and a transport zone. Therefore, perturbation of placental endocrine function by ER stress can be generated without directly affecting its capacity for nutrient exchange. In this review, we summarise the current literature on how transgenic mouse models enhance our understanding of ER stress-mediated perturbation of placental endocrine function, and its contribution to the pathophysiology of pregnancy complications and life-long health.<\/jats:p>","DOI":"10.3390\/cells15020096","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"96","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering Roles of Placental Endoplasmic Reticulum Stress in Complicated Pregnancies and Beyond: The Power of Mouse Models"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-7426","authenticated-orcid":false,"given":"Hong Wa","family":"Yung","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge CB2 0SW, UK"},{"name":"Loke Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8776-4034","authenticated-orcid":false,"given":"Yat Nam","family":"Yung","sequence":"additional","affiliation":[{"name":"Gonville and Caius College, University of Cambridge, Cambridge CB2 1TA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8677-4143","authenticated-orcid":false,"given":"Graham J.","family":"Burton","sequence":"additional","affiliation":[{"name":"Loke Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-4890","authenticated-orcid":false,"given":"D. Stephen","family":"Charnock-Jones","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge CB2 0SW, UK"},{"name":"Loke Centre for Trophoblast Research, University of Cambridge, Cambridge CB2 3EG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109050","DOI":"10.1016\/j.diabres.2021.109050","article-title":"IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group\u2019s Criteria","volume":"183","author":"Wang","year":"2022","journal-title":"Diabetes Res. Clin. 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