HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 74/2/403    most recent biolreprod.105.047332v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal My Folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lash, G. E. Articles by Robson, S. C. Search for Related Content PubMed PubMed Citation Articles by Lash, G. E. Articles by Robson, S. C. Agricola Articles by Lash, G. E. Articles by Robson, S. C.

Low Oxygen Concentrations Inhibit Trophoblast Cell Invasion from Early Gestation Placental Explants via Alterations in Levels of the Urokinase Plasminogen Activator System¹

Schools of Surgical and Reproductive Sciences,³ Clinical & Laboratory Sciences,⁴ and Medical Education Development,⁵ University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, NE2 4HH, United Kingdom

ABSTRACT

Extravillous trophoblast cell (EVT) invasion in early pregnancy occurs in a relatively low-oxygen environment. The role of oxygen in regulation of EVT invasion remains controversial. We hypothesized that 1) culture in 3% oxygen inhibits EVT invasion compared with culture at 8% or 20% oxygen and 2) inhibition of invasion is due to alterations in levels of components of the urokinase plasminogen activator (PLAU, uPA) system rather than through increased apoptosis and/or decreased proliferation. Placental samples (8–10, 12–14, and 16–20 wk gestation) were obtained from women undergoing elective surgical termination of pregnancy or after cesarean section delivery (term) at the Royal Victoria Infirmary, Newcastle upon Tyne, U.K. EVT invasion from placental explants cultured at 3%, 8%, or 20% oxygen was assessed using Matrigel invasion assays. Invasion was assessed on Day 6, explants were harvested for analysis of apoptosis and proliferation, and medium was stored for analysis of PLAU system components by ELISA and casein zymography. Culture at 3% oxygen inhibited EVT invasion. PLAU receptor and plasminogen activator inhibitor-2 protein levels were increased and PLAU activity decreased in these cultures. There was no difference in the proliferation in explants cultured at the three different oxygen concentrations. Apoptosis, assessed by M30 immunostaining, was increased in EVT at both 3% and 8% oxygen. The reduction in the invasive capacity of EVT cultured at 3% oxygen appears to be mediated both by a general inhibition of the PLAU system and a decrease in the number of cells available to invade.

apoptosis, early development, explants, implantation, invasion, oxygen, proteases, trophoblast

¹ Supported by funding from BBSRC (S19967).

² Correspondence: Gendie E. Lash, School of Surgical and Reproductive Sciences, 3rd Floor, William Leech Building, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, U.K. FAX: 44 191 222 5066; g.e.lash{at}ncl.ac.uk

This article has been cited by other articles:

				P. Paiva, L. A. Salamonsen, U. Manuelpillai, and E. Dimitriadis Interleukin 11 Inhibits Human Trophoblast Invasion Indicating a Likely Role in the Decidual Restraint of Trophoblast Invasion During Placentation Biol Reprod, February 1, 2009; 80(2): 302 - 310. [Abstract] [Full Text] [PDF]

				T. W. Bonagura, G. J. Pepe, A. C. Enders, and E. D. Albrecht Suppression of Extravillous Trophoblast Vascular Endothelial Growth Factor Expression and Uterine Spiral Artery Invasion by Estrogen during Early Baboon Pregnancy Endocrinology, October 1, 2008; 149(10): 5078 - 5087. [Abstract] [Full Text] [PDF]

				S.K.M. Seeho, J.H. Park, J. Rowe, J.M. Morris, and E.D.M. Gallery Villous explant culture using early gestation tissue from ongoing pregnancies with known normal outcomes: the effect of oxygen on trophoblast outgrowth and migration Hum. Reprod., May 1, 2008; 23(5): 1170 - 1179. [Abstract] [Full Text] [PDF]