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Hum. Reprod. Advance Access published online on March 5, 2008

Human Reproduction, doi:10.1093/humrep/den066
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Villous explant culture using early gestation tissue from ongoing pregnancies with known normal outcomes: the effect of oxygen on trophoblast outgrowth and migration

S.K.M. Seeho1, J.H. Park, J. Rowe, J.M. Morris and E.D.M. Gallery

Perinatal Research, Kolling Institute of Medical Research, The University of Sydney, Northern Clinical School, St Leonards, NSW 2065, Australia

1 Correspondence address. Fax: +61-2-99268880; E-mail: seanseeho{at}med.usyd.edu.au/ sean_seeho{at}hotmail.com

BACKGROUND: Early placental and embryo development occur in a physiologically low oxygen environment, with a rise in oxygen tension within the placenta towards the end of the first trimester. Oxygen is implicated in the regulation of trophoblast differentiation and invasion. This study examined the effects of oxygen tension on extravillous trophoblast outgrowth and migration from normal pregnancies free of significant pathology.

METHODS: Early gestation villous tissue (11–14 weeks gestation), obtained by chorionic villus sampling, was cultured in 3 or 20% oxygen. Maternal and fetal outcomes were ascertained for all samples. The frequency and amount of trophoblast outgrowth and migration from villi were measured for up to 192 h.

RESULTS: Significantly fewer explants produced outgrowths in 3% compared with 20% oxygen. The number of sites of trophoblast outgrowth and the extent of migration were also significantly less in 3% compared with 20% oxygen. In vitro hypoxia/reoxygenation further reduced trophoblast growth compared with 3% oxygen alone. HLA-G expression in extravillous trophoblasts was not affected by oxygen tension, with HLA-G positive extravillous trophoblasts being universally Ki67 negative.

CONCLUSION: Human placental villi and extravillous trophoblasts in the late first trimester of pregnancy are sensitive to oxygen tension, with low oxygen inhibiting extravillous trophoblast outgrowth and migration.

Key words: chorionic villus sampling/migration/outgrowth/oxygen/trophoblast

Submitted on September 5, 2007; resubmitted on February 3, 2008; accepted on February 11, 2008.


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