Uterine injury during diestrus leads to placental and embryonic defects in future pregnancies in mice†.
Uterine injury during diestrus leads to placental and embryonic defects in future pregnancies in mice†.
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发情间期的子宫损伤会导致小鼠在未来怀孕时出现胎盘和胚胎缺陷。
DOI：
10.1093/biolre/ioae001
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发表时间：
2024
影响因子：
3.6
通讯作者：
Baker,JulieC
中科院分区：
文献类型：
--
作者：
Zhang,ElisaT;Wells,KristenL;Bergman,AbbyJ;Ryan,EmilyE;Steinmetz,LarsM;Baker,JulieC
剖宫产等手术造成的子宫损伤通常会对随后的妊娠结局造成严重后果，导致前置胎盘、胎盘增生和不孕症等疾病。在美国，剖腹产率约占分娩的30%，并且预计将继续攀升，因此需要更深入地了解这些妊娠障碍产生的机制和干预的机会。在这里，我们描述了一个啮齿动物的子宫损伤模型对随后的子宫结局。我们观察到三种不同的表型：吸收率和死亡率增加，胚胎间距缺陷，蜕膜减少和侵袭性滋养细胞扩张的胎盘增生样特征。我们发现胚胎间距缺陷的出现完全取决于损伤时的发情周期阶段。利用RNA-seq，我们发现了损伤恢复后COX/前列腺素通路组分表达的扰动，这一途径先前已被证明在胚胎间隔中起重要作用。因此，我们证明，在这种小鼠模型中，子宫损伤引起形态学和分子变化，最终导致胎盘和胚胎发育缺陷。
Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at ~30% of deliveries in the USA and projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. Here we describe a rodent model of uterine injury on subsequentin uterooutcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes that ultimately lead to placental and embryonic developmental defects.