{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:03:36Z","timestamp":1793120616374,"version":"4.5.0"},"reference-count":79,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["NIH P20 GM121298"],"award-info":[{"award-number":["NIH P20 GM121298"]}]},{"name":"National Institute of Health","award":["P30 GM114750"],"award-info":[{"award-number":["P30 GM114750"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have previously described that placental activation of autophagy is a central feature of normal pregnancy, whereas autophagy is impaired in preeclampsia (PE). Here, we show that hypoxia\u2013reoxygenation (H\/R) treatment dysregulates key molecules that maintain autophagy\u2013lysosomal flux in primary human trophoblasts (PHTs). Ultrastructural analysis using transmission electron microscopy reveals a significant reduction in autophagosomes and autolysosomes in H\/R-exposed PHTs. H\/R-induced accumulation of protein aggregates follows a similar pattern that occurs in PHTs treated with a lysosomal disruptor, chloroquine. Importantly, the placenta from early-onset PE deliveries exhibits the same features as seen in H\/R-treated PHTs. Taken together, our results indicate that H\/R disrupts autophagic machinery in PHTs and that impaired autophagy in the placenta from early-onset PE deliveries mimics the events in H\/R-treated PHTs. Notably, assessment of key regulators at each stage of autophagic processes, especially lysosomal integrity, and verification of autophagic ultrastructure are essential for an accurate evaluation of autophagy activity in human trophoblasts and placental tissue from PE deliveries.<\/jats:p>","DOI":"10.3390\/ijms23105644","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T11:59:37Z","timestamp":1652875177000},"page":"5644","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Hypoxia-Reoxygenation Impairs Autophagy-Lysosomal Machinery in Primary Human Trophoblasts Mimicking Placental Pathology of Early-Onset Preeclampsia"],"prefix":"10.3390","volume":"23","author":[{"given":"Shibin","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheping","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanta","family":"Jash","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3814-8943","authenticated-orcid":false,"given":"Kathleen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8940-3708","authenticated-orcid":false,"given":"Shigeru","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 30-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitoshi","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 30-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4331-3467","authenticated-orcid":false,"given":"Surendra","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Women & Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, Providence, RI 02905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.cell.2007.02.023","article-title":"Autophagy: Paying Charon\u2019s toll","volume":"128","author":"Yoshimori","year":"2007","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4161\/auto.1.3.2017","article-title":"Autophagy and aging: The importance of maintaining \u201cclean\u201d cells","volume":"1","author":"Cuervo","year":"2005","journal-title":"Autophagy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/s41556-018-0201-5","article-title":"Life, death and autophagy","volume":"20","author":"Doherty","year":"2018","journal-title":"Nat. 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