Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China.
Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou, China.
Am J Reprod Immunol. 2020 Sep;84(3):e13283. doi: 10.1111/aji.13283. Epub 2020 Jul 11.
Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that infections might play a significant and potentially preventable cause of premature birth. This work assessed the effects of erythropoietin (EPO) in a murine model of inflammation-associated preterm delivery, which mimics central features of preterm infections in humans.
BALB/c mice were injected i.p. with 20 000 IU/kg EPO or normal saline twice on gestational day (GD) 15, with a 3 hours time interval between injections. An hour after the first EPO or normal saline injection, all mice received two injections of 50 μg/kg LPS, also given 3 hours apart.
EPO significantly prevented preterm labor and increased offspring survival in an LPS induced preterm delivery model. EPO prevented LPS-induced leukocyte infiltration into the placenta. Moreover, EPO inhibited the expression of pro-inflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α) in maternal serum and amniotic fluid. EPO also prevented LPS-induced increase in placental prostaglandin (PG)E2 and uterine inducible nitric oxide synthase (iNOS) production, while decreasing nuclear factor kappa-B (NF-κβ) activity in the myometrium. EPO also increased the gene expression of placental programmed cell death ligand 1 (PD-L1) in LPS-treated mice.
Our results suggest that EPO could be a potential novel therapeutic strategy to tackle infection-related preterm labor.
早产是新生儿死亡的主要原因，并导致儿童身体和认知发育迟缓。目前，尚无有效的疗法来预防早产。大量证据表明，感染可能是导致早产的一个重要且潜在可预防的原因。本研究评估了促红细胞生成素（EPO）在模拟人类早产感染的炎症相关早产小鼠模型中的作用。
BALB/c 小鼠在妊娠第 15 天两次经腹腔注射 20000IU/kg EPO 或生理盐水，两次注射之间间隔 3 小时。第一次 EPO 或生理盐水注射后 1 小时，所有小鼠均接受两次 50μg/kg LPS 注射，两次注射间隔 3 小时。
EPO 显著预防了 LPS 诱导的早产，并增加了早产模型中后代的存活率。EPO 可预防 LPS 诱导的白细胞浸润胎盘。此外，EPO 抑制了母血清和羊水中促炎细胞因子白细胞介素 1β（IL-1β）、白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）的表达。EPO 还可预防 LPS 诱导的胎盘前列腺素（PG）E2 和子宫诱导型一氧化氮合酶（iNOS）产生增加，同时降低子宫肌层核因子 kappa-B（NF-κβ）活性。EPO 还增加了 LPS 处理小鼠胎盘程序性细胞死亡配体 1（PD-L1）的基因表达。
我们的研究结果表明，EPO 可能是一种治疗与感染相关的早产的潜在新策略。
