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The impact of ionizing radiation on placental trophoblasts

Identifieur interne : 004E12 ( Main/Exploration ); précédent : 004E11; suivant : 004E13

The impact of ionizing radiation on placental trophoblasts

Auteurs : D. J. Kanter [États-Unis] ; M. B. O'Brien [États-Unis] ; X.-H. Shi [États-Unis] ; T. Chu [États-Unis] ; T. Mishima [États-Unis] ; S. Beriwal [États-Unis] ; M. W. Epperly [États-Unis] ; Peter Wipf [États-Unis] ; J. S. Greenberger [États-Unis] ; Y. Sadovsky [États-Unis]

Source :

RBID : Pascal:15-0012831

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English descriptors

Abstract

Introduction: Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth. Methods: Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury. Results: We found that survival of in vitro-irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta. Discussion and conclusion: While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation.

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<imprint>
<date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">Placenta : (Eastbourne)</title>
<title level="j" type="abbreviated">Placenta : (Eastbourne)</title>
<idno type="ISSN">0143-4004</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Animals</term>
<term>Cell Line</term>
<term>Female</term>
<term>Fetal Development (radiation effects)</term>
<term>Fetal Growth Retardation (etiology)</term>
<term>Gene Expression Regulation, Developmental (radiation effects)</term>
<term>Humans</term>
<term>Ionizing radiation</term>
<term>Mammalia</term>
<term>Mice</term>
<term>Nitrogen Oxides (therapeutic use)</term>
<term>Placenta</term>
<term>Placenta (radiation effects)</term>
<term>Pregnancy</term>
<term>Radiation Injuries (drug therapy)</term>
<term>Radiation, Ionizing</term>
<term>Trophoblaste</term>
<term>Trophoblasts (radiation effects)</term>
<term>Whole-Body Irradiation (adverse effects)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Animaux</term>
<term>Développement foetal (effets des radiations)</term>
<term>Femelle</term>
<term>Grossesse</term>
<term>Humains</term>
<term>Irradiation corporelle totale (effets indésirables)</term>
<term>Lignée cellulaire</term>
<term>Lésions radio-induites (traitement médicamenteux)</term>
<term>Oxydes d'azote (usage thérapeutique)</term>
<term>Placenta (effets des radiations)</term>
<term>Rayonnement ionisant</term>
<term>Retard de croissance intra-utérin (étiologie)</term>
<term>Régulation de l'expression des gènes au cours du développement (effets des radiations)</term>
<term>Souris</term>
<term>Trophoblastes (effets des radiations)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Nitrogen Oxides</term>
</keywords>
<keywords scheme="MESH" qualifier="adverse effects" xml:lang="en">
<term>Whole-Body Irradiation</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Radiation Injuries</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des radiations" xml:lang="fr">
<term>Développement foetal</term>
<term>Placenta</term>
<term>Régulation de l'expression des gènes au cours du développement</term>
<term>Trophoblastes</term>
</keywords>
<keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr">
<term>Irradiation corporelle totale</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en">
<term>Fetal Growth Retardation</term>
</keywords>
<keywords scheme="MESH" qualifier="radiation effects" xml:lang="en">
<term>Fetal Development</term>
<term>Gene Expression Regulation, Developmental</term>
<term>Placenta</term>
<term>Trophoblasts</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Lésions radio-induites</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Oxydes d'azote</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr">
<term>Retard de croissance intra-utérin</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Animals</term>
<term>Cell Line</term>
<term>Female</term>
<term>Humans</term>
<term>Mice</term>
<term>Pregnancy</term>
<term>Radiation, Ionizing</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Animaux</term>
<term>Femelle</term>
<term>Grossesse</term>
<term>Humains</term>
<term>Lignée cellulaire</term>
<term>Rayonnement ionisant</term>
<term>Placenta</term>
<term>Souris</term>
<term>Trophoblaste</term>
<term>Mammalia</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr">
<term>Rayonnement ionisant</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Introduction: Exposure to low-dose radiation is widespread and attributable to natural sources. However, occupational, medical, accidental, and terrorist-related exposures remain a significant threat. Information on radiation injury to the feto-placental unit is scant and largely observational. We hypothesized that radiation causes trophoblast injury, and alters the expression of injury-related transcripts in vitro or in vivo, thus affecting fetal growth. Methods: Primary human trophoblasts (PHTs), BeWo or NCCIT cells were irradiated in vitro, and cell number and viability were determined. Pregnant C57Bl/6HNsd mice were externally irradiated on E13.5, and placentas examined on E17.5. RNA expression was analyzed using microarrays and RT-qPCR. The experiments were repeated in the presence of the gramicidin S (GS)-derived nitroxide JP4-039, used to mitigate radiation-induced cell injury. Results: We found that survival of in vitro-irradiated PHT cell was better than that of irradiated BeWo trophoblast cell line or the radiosensitive NCCIT mixed germ cell tumor line. Radiation altered the expression of several trophoblast genes, with a most dramatic effect on CDKN1A (p21, CIP1). Mice exposed to radiation at E13.5 exhibited a 25% reduction in mean weight by E17.5, and a 9% reduction in placental weight, which was associated with relatively small changes in placental gene expression. JP4-039 had a minimal effect on feto-placental growth or on gene expression in irradiated PHT cells or mouse placenta. Discussion and conclusion: While radiation affects placental trophoblasts, the established placenta is fairly resistant to radiation, and changes in this tissue may not fully account for fetal growth restriction induced by ionizing radiation.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>États-Unis</li>
</country>
<region>
<li>Pennsylvanie</li>
</region>
<settlement>
<li>Pittsburgh</li>
</settlement>
<orgName>
<li>Université de Pittsburgh</li>
</orgName>
</list>
<tree>
<country name="États-Unis">
<region name="Pennsylvanie">
<name sortKey="Kanter, D J" sort="Kanter, D J" uniqKey="Kanter D" first="D. J." last="Kanter">D. J. Kanter</name>
</region>
<name sortKey="Beriwal, S" sort="Beriwal, S" uniqKey="Beriwal S" first="S." last="Beriwal">S. Beriwal</name>
<name sortKey="Chu, T" sort="Chu, T" uniqKey="Chu T" first="T." last="Chu">T. Chu</name>
<name sortKey="Epperly, M W" sort="Epperly, M W" uniqKey="Epperly M" first="M. W." last="Epperly">M. W. Epperly</name>
<name sortKey="Greenberger, J S" sort="Greenberger, J S" uniqKey="Greenberger J" first="J. S." last="Greenberger">J. S. Greenberger</name>
<name sortKey="Mishima, T" sort="Mishima, T" uniqKey="Mishima T" first="T." last="Mishima">T. Mishima</name>
<name sortKey="O Brien, M B" sort="O Brien, M B" uniqKey="O Brien M" first="M. B." last="O'Brien">M. B. O'Brien</name>
<name sortKey="Sadovsky, Y" sort="Sadovsky, Y" uniqKey="Sadovsky Y" first="Y." last="Sadovsky">Y. Sadovsky</name>
<name sortKey="Sadovsky, Y" sort="Sadovsky, Y" uniqKey="Sadovsky Y" first="Y." last="Sadovsky">Y. Sadovsky</name>
<name sortKey="Shi, X H" sort="Shi, X H" uniqKey="Shi X" first="X.-H." last="Shi">X.-H. Shi</name>
<name sortKey="Wipf, P" sort="Wipf, P" uniqKey="Wipf P" first="P." last="Wipf">Peter Wipf</name>
</country>
</tree>
</affiliations>
</record>

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