Interleukin 33 (IL33) signaling has been implicated in the establishment and maintenance of pregnancy and in pregnancy disorders. The goal of this project was to evaluate the role of IL33 signaling in rat pregnancy. The rat possesses hemochorial placentation with deep intrauterine trophoblast invasion; features also characteristic of human placentation. We generated and characterized a germline mutant rat model for IL33 using CRISPR/Cas9 genome editing. IL33 deficient rats exhibited deficits in lung responses to an inflammatory stimulus (Sephadex G-200) and to estrogen-induced uterine eosinophilia. Female rats deficient in IL33 were fertile and exhibited pregnancy outcomes (gestation length and litter size) similar to wild-type rats. Placental weight was adversely affected by the disruption of IL33 signaling. A difference in pregnancy-dependent adaptations to lipopolysaccharide (LPS) exposure was observed between wild-type and IL33 deficient pregnancies. Pregnancy in wild-type rats treated with LPS did not differ significantly from pregnancy in vehicle-treated wild-type rats. In contrast, LPS treatment decreased fetal survival rate, fetal and placental weights, and increased fetal growth restriction in IL33 deficient rats. In summary, a new rat model for investigating IL33 signaling has been established. IL33 signaling participates in the regulation of placental development and protection against LPS-induced fetal and placental growth restriction.

中文翻译：

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IL33 信号传导在与脂多糖暴露相关的阴性妊娠结局中的保护作用

白细胞介素 33 (IL33) 信号传导与妊娠的建立和维持以及妊娠疾病有关。该项目的目标是评估 IL33 信号传导在大鼠妊娠中的作用。大鼠具有血绒质胎盘，子宫内滋养层深部浸润；特征也是人类胎盘的特征。我们使用 CRISPR/Cas9 基因组编辑生成并表征了 IL33 种系突变大鼠模型。IL33缺陷的大鼠表现出肺部对炎症刺激物（Sephadex G-200）和雌激素诱导的子宫嗜酸性粒细胞增多的反应缺陷。缺乏 IL33 的雌性大鼠具有生育能力，并且表现出与野生型大鼠相似的妊娠结局（妊娠长度和产仔数）。IL33 信号传导的破坏对胎盘重量产生不利影响。在野生型和 IL33 缺陷型妊娠之间观察到妊娠依赖性对脂多糖 (LPS) 暴露的适应存在差异。用 LPS 处理的野生型大鼠的妊娠与用媒介物处理的野生型大鼠的妊娠没有显着差异。相反，LPS治疗降低了IL33缺陷大鼠的胎儿存活率、胎儿和胎盘重量，并增加了胎儿生长受限。总之，已经建立了用于研究 IL33 信号传导的新大鼠模型。IL33 信号传导参与胎盘发育的调节和针对 LPS 诱导的胎儿和胎盘生长受限的保护。用 LPS 处理的野生型大鼠的妊娠与用媒介物处理的野生型大鼠的妊娠没有显着差异。相反，LPS治疗降低了IL33缺陷大鼠的胎儿存活率、胎儿和胎盘重量，并增加了胎儿生长受限。总之，用于研究 IL33 信号传导的新大鼠模型已经建立。IL33 信号传导参与胎盘发育的调节和针对 LPS 诱导的胎儿和胎盘生长受限的保护。用 LPS 处理的野生型大鼠的妊娠与用媒介物处理的野生型大鼠的妊娠没有显着差异。相反，LPS治疗降低了IL33缺陷大鼠的胎儿存活率、胎儿和胎盘重量，并增加了胎儿生长受限。总之，已经建立了用于研究 IL33 信号传导的新大鼠模型。IL33 信号传导参与胎盘发育的调节和针对 LPS 诱导的胎儿和胎盘生长受限的保护。