IFN-gamma promotes apoptosis of the uterus and placenta in pregnant rat and human cytotrophoblast cells.
Growth and development of placentas in all pregnancy periods and that of fetuses in late pregnancy were inhibited after administration of interferon-gamma (IFN-gamma). Apoptosis can be detected by TUNEL at the maternal-fetal interface during normal rat pregnancy. Apoptosis locations at the maternal-fetal interface changed according to the period of pregnancy. The results of immunohistochemistry and the DNA ladder assay showed that IFN-gamma could promote the apoptosis levels during the entire pregnancy, but it did not change the apoptosis locations. IFN regulatory factor-1 (IRF-1), FasL, and p53 expressions were modulated by IFN-gamma during the entire pregnancy. In vitro cell proliferation assay indicated that IFN-gamma could inhibit proliferation of human cytotrophoblast cells, and flow assay showed that this effect was mainly due to apoptosis induction. TUNEL and Hoechst staining also showed that IFN-gamma could induce apoptosis of human cytotrophoblast cells. Expression of IRF-1 was induced and expression of active caspase-3 was promoted by IFN-gamma treatment, but IFN-gamma did not affect the expression of IFNGR and p53.
Sun
Quan-Hong
QH
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, P.R. China.
Peng
Jing-Pian
JP
Xia
Hong-Fei
HF
Yang
Ying
Y
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D010920:Placenta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D014327:Trophoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014599:Uterus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D011994:Recombinant Proteins; D007371:Interferon-gamma