| First Author | Munisha M | Year | 2026 |
| Journal | PLoS Genet | Volume | 22 |
| Issue | 4 | Pages | e1012111 |
| PubMed ID | 41973757 | Mgi Jnum | J:383439 |
| Mgi Id | MGI:8325497 | Doi | 10.1371/journal.pgen.1012111 |
| Citation | Munisha M, et al. (2026) Chronic replication stress-mediated genomic instability disrupts placenta development in mice. PLoS Genet 22(4):e1012111 |
| abstractText | 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, it was reduced in the JZ 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 (ESCs) 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. |
