PMID- 32506750 OWN - NLM STAT- MEDLINE DCOM- 20210902 LR - 20210902 IS - 1600-0897 (Electronic) IS - 1046-7408 (Print) IS - 1046-7408 (Linking) VI - 84 IP - 3 DP - 2020 Sep TI - Erythropoietin prevents LPS-induced preterm birth and increases offspring survival. PG - e13283 LID - 10.1111/aji.13283 [doi] LID - e13283 AB - 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 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 mug/kg LPS, also given 3 hours 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-1beta (IL-1beta), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha) 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-kappabeta) 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. CI - (c) 2020 The Authors. American Journal of Reproductive Immunology published by John Wiley & Sons Ltd. FAU - Zhang, Jie AU - Zhang J AUID- ORCID: 0000-0002-3935-5883 AD - Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Luo, Xianqiong AU - Luo X AD - Department of Pediatrics, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Huang, Caicai AU - Huang C AD - Department of Obstetrics, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Pei, Zheng AU - Pei Z AD - Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Xiao, Huimei AU - Xiao H AD - Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Luo, Xingang AU - Luo X AD - Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Huang, Shuangmiao AU - Huang S AD - Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China. FAU - Chang, Yanqun AU - Chang Y AD - Department of Rehabilitation, Guangdong Women and Children Hospital, Guangzhou, China. LA - eng PT - Journal Article DEP - 20200711 PL - Denmark TA - Am J Reprod Immunol JT - American journal of reproductive immunology (New York, N.Y. : 1989) JID - 8912860 RN - 0 (B7-H1 Antigen) RN - 0 (Cd274 protein, mouse) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 11096-26-7 (Erythropoietin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, mouse) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Amniotic Fluid/immunology MH - Animals MH - B7-H1 Antigen/immunology MH - Cytokines/blood MH - Dinoprostone/immunology MH - Erythropoietin/*therapeutic use MH - Female MH - Leukocytes/drug effects/immunology MH - Lipopolysaccharides MH - Mice, Inbred BALB C MH - NF-kappa B/immunology MH - Nitric Oxide Synthase Type II/immunology MH - Placenta/drug effects/immunology MH - Pregnancy MH - Pregnancy Complications, Infectious/immunology/*prevention & control MH - Premature Birth/chemically induced/immunology/*prevention & control PMC - PMC7507205 OTO - NOTNLM OT - PDL1 OT - erythropoietin OT - inflammation OT - offspring survival OT - preterm birth OT - prostaglandins COIS- The authors declare that they have no conflict of interest. EDAT- 2020/06/09 06:00 MHDA- 2021/09/03 06:00 PMCR- 2020/09/22 CRDT- 2020/06/08 06:00 PHST- 2019/11/27 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/06/01 00:00 [accepted] PHST- 2020/06/09 06:00 [pubmed] PHST- 2021/09/03 06:00 [medline] PHST- 2020/06/08 06:00 [entrez] PHST- 2020/09/22 00:00 [pmc-release] AID - AJI13283 [pii] AID - 10.1111/aji.13283 [doi] PST - ppublish SO - Am J Reprod Immunol. 2020 Sep;84(3):e13283. doi: 10.1111/aji.13283. Epub 2020 Jul 11.