女性癌症幸存者比普通人更容易经历不孕症。化疗和放疗有可能损害卵巢并损害生育能力，但是癌症治疗导致子宫损害的能力、以及其中的机制尚未得到充分研究。本研究表明，全身γ射线（TBI）会在小鼠子宫细胞中引起广泛的DNA损伤和细胞凋亡。之后，我们将健康的供体胚胎移植到先前暴露于TBI的卵巢切除的青春期雌性小鼠中，以研究放射治疗对子宫的影响，而排除对卵巢内分泌功能的影响。TBI后，虽然胚胎着床并移植没有受到影响，但在妊娠中期，100％的母鼠都出现了胎儿吸收的情况，暗示胎盘发育失败。与此假设一致，TBI影响了小鼠和人类内膜间质细胞的蜕膜反应。TBI还导致子宫动脉内皮功能障碍，可能阻止了孕早期充分的血管重塑。值得注意的是，当Puma缺陷（Puma- / -）的小鼠受到TBI影响时，子宫内细胞的凋亡被防止，且蜕膜化、血管功能和妊娠得到恢复，从而证明PUMA介导的细胞凋亡是一个关键的机制。总之，这些数据表明TBI会损害子宫并影响怀孕成功率，因此在放疗期间实现最佳生育保护可能需要保护卵巢和子宫两者。在这方面，抑制PUMA可能代表一种潜在的生育保护策略。

Female cancer survivors are significantly more likely to experience infertility than the general population. It is well established that chemotherapy and radiotherapy can damage the ovary and compromise fertility, yet the ability of cancer treatments to induce uterine damage, and the underlying mechanisms, have been understudied. Here, we show that in mice total-body γ-irradiation (TBI) induced extensive DNA damage and apoptosis in uterine cells. We then transferred healthy donor embryos into ovariectomized adolescent female mice that were previously exposed to TBI to study the impacts of radiotherapy on the uterus independent from effects to ovarian endocrine function. Following TBI, embryo attachment and implantation were unaffected, but fetal resorption was evident at midgestation in 100% of dams, suggesting failed placental development. Consistent with this hypothesis, TBI impaired the decidual response in mice and primary human endometrial stromal cells. TBI also caused uterine artery endothelial dysfunction, likely preventing adequate blood vessel remodeling in early pregnancy. Notably, when pro-apoptotic protein Puma-deficient (Puma-/-) mice were exposed to TBI, apoptosis within the uterus was prevented, and decidualization, vascular function, and pregnancy were restored, identifying PUMA-mediated apoptosis as a key mechanism. Collectively, these data show that TBI damages the uterus and compromises pregnancy success, suggesting that optimal fertility preservation during radiotherapy may require protection of both the ovaries and uterus. In this regard, inhibition of PUMA may represent a potential fertility preservation strategy.