{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:44:03Z","timestamp":1776797043840,"version":"3.51.2"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012111","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["5R01HD107910"],"award-info":[{"award-number":["5R01HD107910"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003194","name":"New York Stem Cell Foundation","doi-asserted-by":"publisher","award":["Druckenmiller Postdoc Fellowship"],"award-info":[{"award-number":["Druckenmiller Postdoc Fellowship"]}],"id":[{"id":"10.13039\/100003194","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012756","name":"Lalor Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012756","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>Abnormal placentation drives many pregnancy-related pathologies and poor fetal outcomes, but the underlying molecular causes are understudied. Here, we show that persistent replication stress due to mutations in the MCM2\u20137 replicative helicase disrupts placentation and reduces embryo viability in mice. MCM-deficient embryos exhibited normal morphology, but their placentae had a drastically diminished junctional zone (JZ). Whereas cell proliferation in the labyrinth zone (LZ) remained unaffected, it was reduced in the JZ during development. MCM2\u20137 deficient trophoblast stem cells (TSCs) failed to maintain stemness, suggesting that replication stress affects the initial trophoblast progenitor pool in a manner that preferentially impacts the developing JZ. In contrast, pluripotency of mouse embryonic stem cells (ESCs) with MCM2\u20137 deficiency were not affected. Developing female mice deficient for FANCM, a protein involved in replication-associated DNA repair, also had placentae with a diminished JZ. These findings indicate that replication stress-induced genomic instability compromises embryo outcomes by impairing placentation.<\/jats:p>","DOI":"10.1371\/journal.pgen.1012111","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T17:37:23Z","timestamp":1776101843000},"page":"e1012111","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic replication stress-mediated genomic instability disrupts placenta development in 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