Differential effects of CpG TLR9 axis on pregnancy outcome in nonobese diabetic mice and wild type controls

CpG-driven innate immune activation can cause activation and amplification of macrophages followed by their migration to the fetomaternal microenvironment, up-regulated tumor necrosis factor-a production, and consequent adverse outcomes of pregnancy.

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Yun Sun M.D., Xiaoli Qin, M.D., Bin Shan M.D., Wenjing Wang, M.S., Qinling Zhu, M.S., Surendra Sharma, M.D., Ph.D., Ji Wu, Ph.D., Yi Lin, M.D.

Volume 99, Issue 6, Pages 1759-1767.e4, May 2013



To elucidating the relationship between CpG-induced activation of innate immunity and pregnancy outcome.


An animal model-based study.




Pregnant nonobese diabetic (NOD) mice were compared with nonimmunodeficient mice.


We mimic TLR9 activation using CpG ODN administration in pregnant wild-type (WT) and NK cell deficiency NOD mice.

Main Outcome Measure:

Evaluation of fetal resorption and preterm birth in pregnant mice. Flow cytometric analysis and ELISA detection.


CpG-induced fetal resorption or preterm birth was only observed steadily in NOD mice, but not in WT mice. Concurrently, CpG treatment triggered amplification of uterine macrophages and neutrophils. Moreover, CpG induced a substantial increase of serum mouse keratinocyte-derived cytokine (mKC) and TNF-α that were produced by uterine CD11b+F4/80+ cells, but not NK or CD11b+Gr-1+ cells. In addition, depletion of F4/80+ 56 cells abrogated CpG-induced increase in TNF-α production and improved pregnancy outcomes in NOD mice treated with CpG.


These results provide evidence that CpG-driven innate immune activation may lead to activation and amplification of macrophages followed by their migration to feto-maternal microenvironment, up-regulated TNF-α production and consequent adverse pregnancy outcomes.

Read the full text at: http://www.fertstert.org/article/S0015-0282(13)00177-5/fulltext

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.