Document Detail


Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation.
MedLine Citation:
PMID:  18154598     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PROBLEM: Survivin, a tumor-promoting antiapoptotic molecule, is expressed in the human placenta. Here, we analyzed its expression during normal and pathological murine pregnancy and investigated its participation in human first trimester trophoblast cell survival and proliferation. METHOD OF STUDY: We first analyzed the expression of survivin on the mRNA and protein level at the fetal-maternal interface of normal pregnant (CBA/J x BALB/c) and abortion-prone (CBA/J x DBA/2J) mice at different pregnancy stages by RT-PCR and immunohistochemistry. We also evaluated apoptosis in murine trophoblasts in both mating combinations by TUNEL technique. Functional studies were carried out by knockdown survivin by means of siRNA methodology in two human first trimester trophoblast cell lines [Swan.71 (Sw.71) and HTR8 (H8)]. RESULTS: We observed a peak in mRNA levels on day 5 and a peak of protein levels on day 8 of pregnancy in both combinations. The level of survivin in animals from the abortion-prone group was decreased compared with normal pregnant mice on day 8, which was accompanied by elevated apoptosis rates. In later pregnancy stages (days 10 and 14), survivin levels decreased to levels comparable to those observed right after fecundation in both groups. Transfection of human first trimester cell lines (H8 and Sw.71) with siRNA targeting the survivin gene led to a 76-82% reduction of its expression leading to reduced trophoblast cell viability and proliferation. CONCLUSION: Our findings suggest an important role of survivin to promote trophoblast cell survival and proliferation during placentation, thus maintaining pregnancy. The pregnancy-associated expression of a cancer molecule such as survivin supports the 'pseudo-malignancy' hypothesis of pregnancy. Our data may contribute to the better understanding of trophoblast cell development during implantation and placentation.
Authors:
Stefan Fest; Nadja Brachwitz; Anne Schumacher; Maria Laura Zenclussen; Faisal Khan; Paul O Wafula; Pablo A Casalis; Sara Fill; Serban-Dan Costa; Gil Mor; Hans-Dieter Volk; Holger N Lode; Ana Claudia Zenclussen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of reproductive immunology (New York, N.Y. : 1989)     Volume:  59     ISSN:  1046-7408     ISO Abbreviation:  Am. J. Reprod. Immunol.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-24     Completed Date:  2008-03-31     Revised Date:  2010-08-31    
Medline Journal Info:
Nlm Unique ID:  8912860     Medline TA:  Am J Reprod Immunol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  75-83     Citation Subset:  IM    
Affiliation:
Department of Paediatrics, Charité Universitätsmedizin Berlin, Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Abortion, Spontaneous / metabolism,  physiopathology
Animals
Apoptosis
Cell Line
Cell Proliferation
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Inbred CBA
Mice, Inbred DBA
Microtubule-Associated Proteins / genetics,  metabolism*
Neoplasm Proteins / genetics,  metabolism*
Pregnancy
Pregnancy Outcome
RNA, Messenger / genetics,  metabolism
RNA, Small Interfering / metabolism
Trophoblasts / cytology,  physiology*
Up-Regulation
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Birc5 protein, mouse; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/RNA, Messenger; 0/RNA, Small Interfering

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