Blocking endogenous leukemia inhibitory factor during placental development in mice leads to abnormal placentation and pregnancy loss
- Author(s)
- Winship, A; Correia, J; Krishnan, T; Menkhorst, E; Cuman, C; Zhang, JG; Nicola, NA; Dimitriadis, E;
- Journal Title
- Scientific Reports
- Publication Type
- Journal Article
- Abstract
- The placenta forms the interface between the maternal and fetal circulation and is critical for the establishment of a healthy pregnancy. Specialized trophoblast cells derived from the embryonic trophectoderm play a pivotal role in the establishment of the placenta. Leukemia inhibitory factor (LIF) is one of the predominant cytokines present in the placenta during early pregnancy. LIF has been shown to regulate trophoblast adhesion and invasion in vitro, however its precise role in vivo is unknown. We hypothesized that LIF would be required for normal placental development in mice. LIF and LIFRalpha were immunolocalized to placental trophoblasts and fetal vessels in mouse implantation sites during mid-gestation. Temporally blocking LIF action during specific periods of placental development via intraperitoneal administration of our specific LIFRalpha antagonist, PEGLA, resulted in abnormal placental trophoblast and vascular morphology and reduced activated STAT3 but not ERK. Numerous genes regulating angiogenesis and oxidative stress were altered in the placenta in response to LIF inhibition. Pregnancy viability was also significantly compromised in PEGLA treated mice. Our data suggest that LIF plays an important role in placentation in vivo and the maintenance of healthy pregnancy.
- Publisher
- NPG
- Research Division(s)
- Cancer And Haematology
- PubMed ID
- 26272398
- Publisher's Version
- https://doi.org/10.1038/srep13237
- Open Access at Publisher's Site
http://www.nature.com/articles/srep13237- NHMRC Grants
- NHMRC/550905, NHMRC/637300, NHMRC/611827, NHMRC/1016647,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-08-21 12:29:36
Last Modified: 2015-09-01 03:47:39