{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:35:12Z","timestamp":1790670912540,"version":"4.1.0"},"reference-count":37,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN-04497"],"award-info":[{"award-number":["RGPIN-04497"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["FRN 156081"],"award-info":[{"award-number":["FRN 156081"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Sphingolipids are a class of bioactive signaling lipids that regulate an array of fundamental cellular processes, including cell survival, proliferation and differentiation. Deficiency of acid sphingomyelinase \u2013 an enzyme of the sphingolipid metabolic pathway \u2013 has been previously implicated in human placental pathologies. We demonstrate that acid sphingomyelinase (Smpd1) is required for normal placental development in the mouse, and its deficiency results in an intrauterine growth restriction phenotype. Smpd1-deficient placentas display several anatomical abnormalities, including a reduced labyrinth compartment and increased fetal-maternal interhaemal distance. Finally, we observed several hallmarks of defective autophagy and lysosomal impairment in Smpd1\u2212\/\u2212 placentas, which could explain the inability of Smpd1\u2212\/\u2212 trophoblast to respond to nutrient starvation. Fetal growth restriction could not be rescued by transfer of Smpd1-deficient embryos into a wild-type uterine environment; however, restoration of transcription factor EB phosphorylation was detected. Thus, we conclude that, due to a smaller labyrinthine area, Smpd1 deficiency leads to a decrease in exchange between maternal and fetal blood space, limiting the supply of nutrients to the fetus and resulting in growth restriction.<\/jats:p>","DOI":"10.1242\/dev.204425","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T13:43:58Z","timestamp":1756734238000},"source":"Crossref","is-referenced-by-count":2,"title":["Acid sphingomyelinase is a gatekeeper of placental labyrinthine architecture and function"],"prefix":"10.1242","volume":"152","author":[{"given":"Isidora","family":"Rovic","sequence":"first","affiliation":[{"name":"University of Toronto 1 Department of Physiology, Temerty Faculty of Medicine , , Toronto, Ontario M5S 1A8 ,","place":["Canada"]},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health System 2 , Toronto, Ontario M5G 1X5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Szelag","sequence":"additional","affiliation":[{"name":"University of Toronto 1 Department of Physiology, Temerty Faculty of Medicine , , Toronto, Ontario M5S 1A8 ,","place":["Canada"]},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health System 2 , Toronto, Ontario M5G 1X5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Li","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health System 2 , Toronto, Ontario M5G 1X5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanne","family":"McQuaid","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health System 2 , Toronto, Ontario M5G 1X5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Sugin","sequence":"additional","affiliation":[{"name":"University of Toronto 1 Department of Physiology, Temerty Faculty of Medicine , , Toronto, Ontario M5S 1A8 ,","place":["Canada"]},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health System 2 , Toronto, Ontario M5G 1X5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Que","family":"Wu","sequence":"additional","affiliation":[{"name":"University of Toronto 1 Department of Physiology, Temerty Faculty of Medicine , , Toronto, Ontario M5S 1A8 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Theodora","sequence":"additional","affiliation":[{"name":"Mouse Imaging Centre 3 , 25 Orde Street, Toronto, Ontario M5T 3H7 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sled","sequence":"additional","affiliation":[{"name":"Mouse Imaging Centre 3 , 25 Orde Street, Toronto, Ontario M5T 3H7 ,","place":["Canada"]},{"name":"Translational Medicine, Hospital for Sick Children 4 , Toronto, Ontario M5G 0A4 ,","place":["Canada"]},{"name":"University Health Network-Toronto General Hospital 5 Department of Medical Biophysics , , Toronto, Ontario M5G 1L7 ,","place":["Canada"]},{"name":"University of Toronto 6 Department of Obstetrics and Gynecology, Temerty Faculty of Medicine , , Toronto, Ontario M5G 1E2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2166-4298","authenticated-orcid":false,"given":"Andrea","family":"Jurisicova","sequence":"additional","affiliation":[{"name":"University of Toronto 1 Department of Physiology, Temerty Faculty of Medicine , , Toronto, Ontario M5S 1A8 ,","place":["Canada"]},{"name":"Lunenfeld-Tanenbaum Research Institute, Sinai Health System 2 , Toronto, Ontario M5G 1X5 ,","place":["Canada"]},{"name":"University of Toronto 6 Department of Obstetrics and Gynecology, Temerty Faculty of Medicine , , Toronto, Ontario M5G 1E2 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"2025100607045032300_DEV204425C1","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1016\/j.placenta.2013.02.004","article-title":"Lipidomic analysis of human placental syncytiotrophoblast microvesicles in adverse pregnancy outcomes","volume":"34","author":"Baig","year":"2013","journal-title":"Placenta"},{"key":"2025100607045032300_DEV204425C2","doi-asserted-by":"publisher","first-page":"S91","DOI":"10.1194\/jlr.R800080-JLR200","article-title":"Bioactive sphingolipids: metabolism and function","volume":"50","author":"Bartke","year":"2009","journal-title":"J. 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