Jie Zhang1, Xianqiong Luo2, Caicai Huang3, Zheng Pei1, Huimei Xiao1, Xingang Luo1, Shuangmiao Huang1, Yanqun Chang1. 1. Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China. 2. Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China. 3. Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, Guangdong, 510010, China.
Abstract
PROBLEM: 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. METHOD OF STUDY: BALB/c mice were injected i.p. with 20000 IU/kg EPO or normal saline twice on gestational day (GD) 15, with a 3 h 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 h apart. RESULTS: 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 tumor 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. CONCLUSIONS: Our results suggest that EPO could be a potential novel therapeutic strategy to tackle infection-related preterm labor. This article is protected by copyright. All rights reserved.
PROBLEM: 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. METHOD OF STUDY: BALB/c mice were injected i.p. with 20000 IU/kg EPO or normal saline twice on gestational day (GD) 15, with a 3 h 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 h apart. RESULTS: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 tumor 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. CONCLUSIONS: Our results suggest that EPO could be a potential novel therapeutic strategy to tackle infection-related preterm labor. This article is protected by copyright. All rights reserved.