Title: | Macrophage depletion and TNF-alpha inhibition prevent resorption in CBA/J x DBA/2 model of CpG-induced abortion |
Address: | "Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, PR China. Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai, 200127, PR China. Electronic address: zamzkh0526@126.com" |
Journal Title: | Biochem Biophys Res Commun |
DOI: | 10.1016/j.bbrc.2015.12.024 |
ISSN/ISBN: | 1090-2104 (Electronic) 0006-291X (Linking) |
Abstract: | "OBJECTIVE: To elucidate the mechanism by which embryo-resorption was enhanced by pathogenic CpG ODN motif in abortion-prone CBA/J x DBA/2 model and to develop a counter strategy for normal pregnancy outcome. METHODS: This is an animal model-based study. Abortion-prone model is established by CBA/J x DBA/2. An infection was mimicked by CpG ODN injection. RESULTS: Embryo-resorption was readily induced by CpG ODN in low doses of CpG ODN ( approximately 25 mug/dam) when intraperitoneally (IP) injected on gestational day(gd) 6.5 in male DBA/2 mated CBA/J female mice. A more modest decline in Progesterone(P4), but not Estrogen(E2) was observed after exposure to CpG ODN in the model. P4 supplement fail to improve pregnancy outcomes, even at pharmocology dose. CpG ODN-induced fetal resorption is prevented by the treatment of anti-F4/80 or by that of anti-TNFalpha.In the implantation sites, the treatment of anti-F4/80 inhibits the increase both of F4/80(+) macrophage proportion and TNF-alphaexpression level which are induced by CpG ODN. The anti-TNFalphatreatment also recovers CpG ODN-induced reduction of CD4(+)Foxp3(+) T cells. CONCLUSION: Circulating P4 is not responsible for the process by which CpG ODN-induced embryonic resorption in an abortion-prone mice. Macrophage depletion and TNF-alpha inhibition are really noteworthy for CpG ODN-induced pregnancy disruption" |
Keywords: | "Animals *CpG Islands *Disease Models, Animal Embryo Loss/chemically induced/*immunology/*prevention & control Female Macrophages/*immunology/pathology Male Mice Mice, Inbred CBA Mice, Inbred DBA Oligodeoxyribonucleotides Pregnancy Pregnancy Outcome Pregna;" |
Notes: | "MedlineKang, Xiaomin Zhang, Xiaoxin Zhao, Aimin eng Research Support, Non-U.S. Gov't 2015/12/22 Biochem Biophys Res Commun. 2016 Jan 15; 469(3):704-10. doi: 10.1016/j.bbrc.2015.12.024. Epub 2015 Dec 12" |