Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia
- PMID:8567979
- PMCID: PMC507049
- DOI: 10.1172/JCI118447
Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia
Abstract
During normal human pregnancy a subpopulation of fetal cytotrophoblast stem cells differentiate and invade the uterus and its arterioles. In the pregnancy disease preeclampsia, cytotrophoblast differentiation is abnormal and invasion is shallow. Thus, the placenta is relatively hypoxic. We investigated whether lowering oxygen tension affects cytotrophoblast differentiation and invasion. Previously we showed that when early gestation cytotrophoblast stem cells are cultured under standard conditions (20% O2) they differentiate/invade, replicating many aspects of the in vivo process. Specifically, the cells proliferate at a low rate and rapidly invade extracellular matrix (ECM) substrates, a phenomenon that requires switching their repertoire of integrin cell-ECM receptors, which are stage-specific antigens that mark specific transitions in the differentiation process. In this study we found that lowering oxygen tension to 2% did not change many of the cells' basic processes. However, there was a marked increase in their incorporation of [3H]thymidine and 5-bromo-2'-deoxyuridine (BrdU). Moreover, they failed to invade ECM substrates, due at least in part to their inability to completely switch their integrin repertoire. These changes mimic many of the alterations in cytotrophoblast differentiation/invasion that occur in preeclampsia, suggesting that oxygen tension plays an important role in regulating these processes in vivo.
Similar articles
- Human cytotrophoblast differentiation/invasion is abnormal in pre-eclampsia.Lim KH, Zhou Y, Janatpour M, McMaster M, Bass K, Chun SH, Fisher SJ.Lim KH, et al.Am J Pathol. 1997 Dec;151(6):1809-18.Am J Pathol. 1997.PMID:9403732Free PMC article.
- Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts.Zhou Y, Damsky CH, Chiu K, Roberts JM, Fisher SJ.Zhou Y, et al.J Clin Invest. 1993 Mar;91(3):950-60. doi: 10.1172/JCI116316.J Clin Invest. 1993.PMID:7680671Free PMC article.
- Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall.DiFederico E, Genbacev O, Fisher SJ.DiFederico E, et al.Am J Pathol. 1999 Jul;155(1):293-301. doi: 10.1016/S0002-9440(10)65123-1.Am J Pathol. 1999.PMID:10393861Free PMC article.
- The placental problem: linking abnormal cytotrophoblast differentiation to the maternal symptoms of preeclampsia.Fisher SJ.Fisher SJ.Reprod Biol Endocrinol. 2004 Jul 5;2:53. doi: 10.1186/1477-7827-2-53.Reprod Biol Endocrinol. 2004.PMID:15236649Free PMC article.Review.
- Placental trophoblast cell differentiation: physiological regulation and pathological relevance to preeclampsia.Ji L, Brkić J, Liu M, Fu G, Peng C, Wang YL.Ji L, et al.Mol Aspects Med. 2013 Oct;34(5):981-1023. doi: 10.1016/j.mam.2012.12.008. Epub 2012 Dec 28.Mol Aspects Med. 2013.PMID:23276825Review.
Cited by
- Human cytomegalovirus infection inhibits CXCL12- mediated migration and invasion of human extravillous cytotrophoblasts.Warner JA, Zwezdaryk KJ, Day B, Sullivan DE, Pridjian G, Morris CA.Warner JA, et al.Virol J. 2012 Nov 1;9:255. doi: 10.1186/1743-422X-9-255.Virol J. 2012.PMID:23116176Free PMC article.
- Human pluripotent stem cells as a model of trophoblast differentiation in both normal development and disease.Horii M, Li Y, Wakeland AK, Pizzo DP, Nelson KK, Sabatini K, Laurent LC, Liu Y, Parast MM.Horii M, et al.Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):E3882-91. doi: 10.1073/pnas.1604747113. Epub 2016 Jun 20.Proc Natl Acad Sci U S A. 2016.PMID:27325764Free PMC article.
- Abnormalities in oxygen sensing define early and late onset preeclampsia as distinct pathologies.Rolfo A, Many A, Racano A, Tal R, Tagliaferro A, Ietta F, Wang J, Post M, Caniggia I.Rolfo A, et al.PLoS One. 2010 Oct 12;5(10):e13288. doi: 10.1371/journal.pone.0013288.PLoS One. 2010.PMID:20967267Free PMC article.
- Sexual dimorphism of mitochondrial function in the hypoxic guinea pig placenta.Song H, Telugu BP, Thompson LP.Song H, et al.Biol Reprod. 2019 Jan 1;100(1):208-216. doi: 10.1093/biolre/ioy167.Biol Reprod. 2019.PMID:30085007Free PMC article.
- Nodal signals through activin receptor-like kinase 7 to inhibit trophoblast migration and invasion: implication in the pathogenesis of preeclampsia.Nadeem L, Munir S, Fu G, Dunk C, Baczyk D, Caniggia I, Lye S, Peng C.Nadeem L, et al.Am J Pathol. 2011 Mar;178(3):1177-89. doi: 10.1016/j.ajpath.2010.11.066.Am J Pathol. 2011.PMID:21356369Free PMC article.
References
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources