Cohesin is an evolutionarily conserved chromosome-associated protein complex essential for chromosome segregation, gene expression, and repair of DNA damage. Mutations that affect this complex cause the human developmental disorder Cornelia de Lange syndrome (CdLS), thought to arise from defective embryonic transcription. We establish a significant role for placental defects in the development of CdLS mouse embryos (Nipbl and Hdac8). Placenta is a naturally senescent tissue; we demonstrate that persistent DNA damage potentiates senescence and activates cytokine signaling. Mutant embryo developmental outcomes are significantly improved in the context of a wild-type placenta or by genetically restricting cytokine signaling. Our study highlights that cohesin is required for maintaining ploidy and the repair of spontaneous DNA damage in placental cells, suggesting that genotoxic stress and ensuing placental senescence and cytokine production could represent a broad theme in embryo health and viability.

粘着蛋白是一种进化保守的染色体相关蛋白复合物，对于染色体分离，基因表达和DNA损伤修复至关重要。影响该复合物的突变会导致人类发育障碍Cornelia de Lange综合征（CdLS），该现象被认为是由缺陷的胚胎转录引起的。我们建立胎盘缺陷在CdLS小鼠胚胎（Nipbl和Hdac8）。胎盘是一种自然衰老的组织。我们证明持续性DNA损伤增强衰老并激活细胞因子信号传导。在野生型胎盘或通过遗传限制细胞因子信号转导的情况下，突变的胚胎发育结果显着改善。我们的研究强调，粘附素是维持胎盘细胞倍性和修复自发性DNA损伤所必需的，这表明遗传毒性应激以及随后的胎盘衰老和细胞因子的产生可能代表着胚胎健康和生存力的广泛主题。