To drive or be driven: the path of a mouse model of recurrent pregnancy loss

Bonney, Elizabeth A.; Brown, Stephen

doi:10.1530/rep-13-0583

Cited by 57 publications

(39 citation statements)

References 158 publications

(186 reference statements)

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“…Pregnancy loss in CBA/J 3 DBA/2 mating combination has been shown to be Ab independent and to be mainly mediated by macrophages and NK cells (29), although the contribution of T cells cannot be excluded. A few years ago, Girardi and colleagues (9) identified the C system as an additional player in the CBA/J 3 DBA/2 model contributing to the high rate of fetal resorption and inducing dysregulation of angiogenic factors.…”

Section: Discussionmentioning

confidence: 99%

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

Petitbarat

Durigutto

Macor

et al. 2015

The Journal of Immunology

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The abortion-prone mating combination CBA/J × DBA/2 has been recognized as a model of preeclampsia, and complement activation has been implicated in the high rate of pregnancy loss observed in CBA/J mice. We have analyzed the implantation sites collected from DBA/2-mated CBA/J mice for the deposition of the complement recognition molecules using CBA/J mated with BALB/c mice as a control group. MBL-A was observed in the implantation sites of CBA/J × DBA/2 combination in the absence of MBL-C and was undetectable in BALB/c-mated CBA/J mice. Conversely, C1q was present in both mating combinations. Searching for other complement components localized at the implantation sites of CBA/J × DBA/2, we found C4 and C3, but we failed to reveal C1r. These data suggest that complement is activated through the lectin pathway and proceeds to completion of the activation sequence as revealed by C9 deposition. MBL-A was detected as early as 3.5 d of pregnancy, and MBL-A deficiency prevented pregnancy loss in the abortion-prone mating combination. The contribution of the terminal complex to miscarriage was supported by the finding that pregnancy failure was largely inhibited by the administration of neutralizing Ab to C5. Treatment of DBA/2-mated CBA/J mice with Polyman2 that binds to MBL-A with high affinity proved to be highly effective in controlling the activation of the lectin pathway and in preventing fetal loss.

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Section: Discussionmentioning

confidence: 99%

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

Petitbarat

Durigutto

Macor

et al. 2015

The Journal of Immunology

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“…The mating of CBA/J female mice with DBA/2J male mice represents a model of immune, rejection-mediated, spontaneous abortion, with an abortion rate of 18-30% under normal conditions [40]. These mice are widely used for studies of fetomaternal immunotolerance, including studies of the roles of NK, macrophages, neutrophils, and T regs in abortion [41]. Based on the observation that depletion of MDSCs caused fetal rejection in healthy pregnancy, we were interested in whether the level of MDSCs was altered in abortion-prone mice.…”

Section: Adoptive Transfer Of G-mdscs Prevents Fetal Rejection In a Mmentioning

confidence: 99%

Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice

Pan

Liu

Zhong

et al. 2016

Journal of Leukocyte Biology

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Maternal immune system tolerance to the semiallogeneic fetus is essential for a successful pregnancy; however, the mechanisms underlying this immunotolerance have not been fully elucidated. Here, we demonstrate that myeloid-derived suppressor cells play an important role in maintaining feto-maternal tolerance. A significant expansion of granulocytic myeloid-derived suppressor cells was observed in multiple immune organs and decidual tissues from pregnant mice. Pregnancy-derived granulocytic myeloid-derived suppressor cells suppressed T cell responses in a reactive oxygen species-dependent manner and required direct cell-cell contact. Mechanistic studies showed that progesterone facilitated differentiation and activation of granulocytic myeloid-derived suppressor cells, mediated through STAT3 signaling. The STAT3 inhibitor JSI-124 and a specific short hairpin RNA completely abrogated the effects of progesterone on granulocytic myeloid-derived suppressor cells. More importantly, granulocytic myeloid-derived suppressor cell depletion dramatically enhanced the abortion rate in normal pregnant mice, whereas adoptive transfer of granulocytic myeloid-derived suppressor cells clearly reduced the abortion rate in the CBA/J X DBA/2J mouse model of spontaneous abortion. These observations collectively demonstrate that granulocytic myeloid-derived suppressor cells play an essential role in the maintenance of fetal immunotolerance in mice. Furthermore, our study supports the notion that in addition to their well-recognized roles under pathologic conditions, myeloid-derived suppressor cells perform important functions under certain physiologic circumstances.

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“…Circulating maternal T reg cells begin to accumulate in mice the day after conception and their numbers increase by approximately two-fold by midgestation during healthy pregnancies 25–27 . By contrast, fetal wastage is associated with defective maternal T reg cell expansion in abortion-prone matings between defined strains of inbred mice, or a reduction in the suppressive capacity of T reg cells on a per cell basis triggered by prenatal infection 28–30 . Allogeneic pregnancies [G] promote a greater expansion of maternal T reg cell populations than syngeneic pregnancies, which highlights the importance of fetal–maternal MHC mismatch in driving maternal T reg cell accumulation 26,27 .…”

Section: Expanded Immune Tolerance During Pregnancymentioning

confidence: 99%

Immunological implications of pregnancy-induced microchimerism

et al. 2017

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Immunological identity is traditionally defined by genetically encoded antigens, with equal maternal and paternal contributions as a result of Mendelian inheritance. However, vertically transferred maternal cells also persist in individuals at very low levels throughout postnatal development. Reciprocally, mothers are seeded during pregnancy with genetically foreign fetal cells that persist long after parturition. Recent findings suggest that these microchimeric cells expressing noninherited familially relevant antigenic traits are not accidental souvenirs of pregnancy, but are purposefully retained within mothers and their offspring to promote genetic fitness by improving the outcome of future pregnancies. Here, we discuss the immunological implications, benefits and potential consequences of individuals being constitutively chimeric with a biologically active ‘microchiome’ of genetically foreign cells.

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To drive or be driven: the path of a mouse model of recurrent pregnancy loss

Abstract: This review is an example of the use of an animal model to try to understand the immune biology of pregnancy. A well-known model of recurrent spontaneous pregnancy loss is put in clinical, historical and theoretical context, with emphasis on T cell biology.

Cited by 57 publications

References 158 publications

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

Critical Role and Therapeutic Control of the Lectin Pathway of Complement Activation in an Abortion-Prone Mouse Mating

Myeloid-derived suppressor cells are essential for maintaining feto-maternal immunotolerance via STAT3 signaling in mice

Immunological implications of pregnancy-induced microchimerism

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