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
- Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure.Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ.Jauniaux E, et al.Am J Pathol. 2000 Dec;157(6):2111-22. doi: 10.1016/S0002-9440(10)64849-3.Am J Pathol. 2000.PMID:11106583Free PMC article.
- Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy.Pringle KG, Kind KL, Sferruzzi-Perri AN, Thompson JG, Roberts CT.Pringle KG, et al.Hum Reprod Update. 2010 Jul-Aug;16(4):415-31. doi: 10.1093/humupd/dmp046. Epub 2009 Nov 19.Hum Reprod Update. 2010.PMID:19926662Free PMC article.Review.
- Regulation of Placental Extravillous Trophoblasts by the Maternal Uterine Environment.Pollheimer J, Vondra S, Baltayeva J, Beristain AG, Knöfler M.Pollheimer J, et al.Front Immunol. 2018 Nov 13;9:2597. doi: 10.3389/fimmu.2018.02597. eCollection 2018.Front Immunol. 2018.PMID:30483261Free PMC article.Review.
- Rosiglitazone blocks first trimester in-vitro placental injury caused by NF-κB-mediated inflammation.Kadam L, Kilburn B, Baczyk D, Kohan-Ghadr HR, Kingdom J, Drewlo S.Kadam L, et al.Sci Rep. 2019 Feb 14;9(1):2018. doi: 10.1038/s41598-018-38336-2.Sci Rep. 2019.PMID:30765769Free PMC article.
- ceRNA Network and Functional Enrichment Analysis of Preeclampsia by Weighted Gene Coexpression Network Analysis.Wang C, Yang C, Wang X, Zhou G, Chen C, Han G.Wang C, et al.Comput Math Methods Med. 2022 Jan 7;2022:5052354. doi: 10.1155/2022/5052354. eCollection 2022.Comput Math Methods Med. 2022.Retraction in:Comput Math Methods Med. 2023 Nov 1;2023:9867945. doi: 10.1155/2023/9867945.PMID:35035521Free PMC article.Retracted.
References
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources