{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:06:15Z","timestamp":1791662775769,"version":"4.3.4"},"reference-count":79,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"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>Successful pregnancy depends on precise placental development, where trophoblast differentiation, syncytialization, invasion, and adaptation to metabolic stress are critical. Autophagy, a lysosome-mediated degradation pathway, has emerged as an important regulator of cellular homeostasis, yet its integrated role in trophoblast fate and functions has not been comprehensively summarised. This review synthesises current evidence on autophagy\u2019s functions throughout placentation, from trophoblast differentiation to syncytialization and extravillous trophoblast invasion. We examine how autophagy enables cellular remodelling during differentiation, supports metabolic adaptation under hypoxia and nutrient stress, and maintains mitochondrial quality control through selective mitophagy. Autophagy is essential for syncytiotrophoblast formation via endoplasmic reticulum stress-coordinated activation and p53 downregulation. However, its effects on trophoblast invasion are context-dependent, influenced by oxygen tension, autophagic flux completeness, and differentiation state, which can potentially be shaped by parent-offspring genetic conflicts through genomic imprinting. Both excessive and insufficient autophagy contribute to pregnancy complications, including pre-eclampsia, foetal growth restriction, gestational diabetes mellitus, preterm birth, recurrent spontaneous abortion and obstetric antiphospholipid syndrome through distinct molecular mechanisms. Autophagy functions as a dynamically tuned homeostatic mechanism in placental development. Understanding condition-specific autophagy dysregulation is thereby crucial for improving pregnancy outcomes.<\/jats:p>","DOI":"10.3390\/cells15171552","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"1552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Autophagy in the Regulation of Placental Development: From Trophoblast Differentiation to Metabolic Stress Adaptation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0784-1739","authenticated-orcid":false,"given":"Chloe","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6153-7245","authenticated-orcid":false,"given":"Hoi Kit Matthew","family":"Leung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6285-8369","authenticated-orcid":false,"given":"Yanjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6808-2139","authenticated-orcid":false,"given":"Sam Chak Sum","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee Tung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4443-1331","authenticated-orcid":false,"given":"Qingqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"},{"name":"School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka-Wang","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C. N.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-3478","authenticated-orcid":false,"given":"Cheuk-Lun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","unstructured":"Herrick, E.J., and Bordoni, B. (2025). Embryology, Placenta. 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