{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:03:47Z","timestamp":1782281027722,"version":"3.54.5"},"posted":{"date-parts":[[2025,3,4]]},"group-title":"Developmental Biology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Child Health and Human Development"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <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 MCM2-7 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, JZ cell proliferation was reduced during development. MCM2-7 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 with MCM2-7 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":"10.1101\/2025.02.28.640689","type":"posted-content","created":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T05:35:37Z","timestamp":1741152937000},"source":"Crossref","is-referenced-by-count":0,"title":["Chronic replication stress-mediated genomic instability disrupts placenta development in mice"],"prefix":"10.64898","author":[{"given":"Mumingjiang","family":"Munisha","sequence":"first","affiliation":[{"name":"Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Huang","sequence":"additional","affiliation":[{"name":"Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Khan","sequence":"additional","affiliation":[{"name":"Cornell University, Meinig School of Biomedical Engineering, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Schimenti","sequence":"additional","affiliation":[{"name":"Cornell University, College of Veterinary Medicine, Department of Biomedical Sciences, Ithaca, NY 14853, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041121302715000_2025.02.28.640689v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dnarep.2021.103195"},{"key":"2026041121302715000_2025.02.28.640689v2.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-072920-022154"},{"key":"2026041121302715000_2025.02.28.640689v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.09.008"},{"key":"2026041121302715000_2025.02.28.640689v2.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-111212-133232"},{"key":"2026041121302715000_2025.02.28.640689v2.5","doi-asserted-by":"crossref","unstructured":"Costanzo, V. , Bardelli, A. , Siena, S. & Abrignani, S . 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