Imaging of Vascular Development in Early Mouse Decidua and Its Association with Leukocytes and Trophoblasts1

Croy, B. Anne; Chen, Zhilin; Hofmann, Alexander P.; Lord, Edith M.; Sedlacek, Abigail L.; Gerber, Scott A.

doi:10.1095/biolreprod.112.102830

Cited by 103 publications

(104 citation statements)

References 52 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…4). Interestingly, neutrophilia has also been observed in human pregnancies (at 11215 wk), as well as in pregnancies of other mouse strains (10,55), which strongly implies a significant role of neutrophils in this period of pregnancy. In fact, neutropenic patients (low neutrophils) have higher spontaneous miscarriage rates (26%).…”

Section: Discussionmentioning

confidence: 80%

Unique Roles of Infiltrating Myeloid Cells in the Murine Uterus during Early to Midpregnancy

Zhao

Kalish

Schulz

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Leukocyte infiltration into the uterus is a characteristic feature in early to midpregnancy, but the composition and function of these leukocytes are not well understood. Using a pregnant murine model, we showed that myeloid cells and uterine NK (uNK) cells were the predominant populations in uteri during early to midgestation, whereas T and B cells were constrained. Uterine myeloid populations included cells that infiltrated from the circulation (myeloid-derived suppressor cells [MDSCs], monocyte-derived macrophages [Mφs], and dendritic cells [DCs]) or proliferated from resident precursors (resident Mφs [Re-Mφs] and DCs). CD11bhiLy6-Ghi cells, representing neutrophils in both blood and uterine MDSCs, significantly increased from embryonic days 8.5 to 9.5. To understand their putative functions, we used anti–Gr-1 Ab to deplete circulating neutrophils and uterine MDSCs. In the absence of MDSC suppression, uterine DCs, T cells, and regulatory T cells expanded. Conversely, uterine MDSCs responded to LPS-induced inflammation and transformed into CD14+-activated neutrophils, resulting in an upregulation of tolerogenic DCs. A high dose of LPS (2.5 μg/mouse) significantly increased the influx of neutrophils and production of proinflammatory cytokines, such as IL-1β and TNF-α, resulting in the reduction of Re-Mφs and uNK cells, and led to placental hemorrhages and fetal deaths. In summary, uterine MDSCs are important in early to midpregnancy by responding to the maternal immunologic milieu and protecting uNK cells and Re-Mφs via MDSC’s suppressive and anti-inflammatory functions. Upsetting this delicate immune balance by factors leading to either insufficient MDSCs or excessive neutrophil infiltration in the fetomaternal interface may contribute to pregnancy failure.

show abstract

Section: Discussionmentioning

confidence: 80%

Unique Roles of Infiltrating Myeloid Cells in the Murine Uterus during Early to Midpregnancy

Zhao

Kalish

Schulz

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Moreover, studies of mouse uterine NK cells showed an increase in the inhibitory receptor KLRG1 with gestational age. 59 KLRG1 is a marker of senescence in mouse and human NK and T cells and is thought to block proliferation by interfering with Akt activation. 60 Thus, there is indirect evidence of a senescent phenotype of the mouse uterine NK cells during the key period of remodeling to permit placental blood flow.…”

Section: A Role For Senescence In Reproductionmentioning

confidence: 99%

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

Rajagopalan

2014

Cell Mol Immunol

View full text Add to dashboard Cite

The uterus in early pregnancy is a non-lymphoid organ that is enriched in natural killer (NK) cells. Studies to address the role of these abundant human NK cells at the maternal/fetal interface have focused on their response to the major histocompatibility complex (MHC) molecules on fetal trophoblast cells that they contact. The interaction of maternal NK cell receptors belonging to the killer cell immunoglobulin-like receptor (KIR) family with trophoblast MHC class I molecules in pregnancy can regulate NK cell activation for secretion of pro-angiogenic factors that promote placental development. This review will cover the role of KIR at the maternal/fetal interface and focus on KIR2DL4, a KIR family member that is uniquely poised to play a role in pregnancy due to the restricted expression of its ligand, human leukocyte antigen (HLA)-G, by fetal trophoblast cells early in pregnancy. The pathways by which KIR2DL4-HLA-G interactions induce the cellular senescence of NK cells and the role of the resulting senescence-associated secretory phenotype (SASP) in vascular remodeling will be discussed in the context of reproduction.

show abstract

“…Gd6.5 uterine horns (n52 pregnancies/genotype) were transected and stained with reagents listed in Table 1 as live, intact tissue as previously described. 32 Specimens were examined and photographed after 60 min using epifluorescence microscopy (Axiovision computer software; Zeiss Axiocam).…”

Section: Morphological Analysesmentioning

confidence: 99%

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Lima

Rahim

et al. 2014

Cell Mol Immunol

View full text Add to dashboard Cite

In humans, specific patterns of killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer (uNK) cells are linked through HLA-C with pregnancy complications (infertility, recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia). To identify mechanisms underpinning the associations between NK cell activation and pregnancy success, pregnancies were studied in mice with genetic knockdown (KD) of the MHC-activated Ly49 receptor gene family. B6.Ly49 KD pregnancies were compared to normal control B6.Ly49 129 and C57BL/6 (B6) pregnancies. At mid-pregnancy (gestation day (gd9.5)), overall uNK cell (TCRb 2 CD122 1 DBA 1 DX5 2 (DBA 1 DX5 2 )) and TCRb 2 CD122 1 DBA 2 DX5 1 (DBA 2 DX5 1 )) frequencies in pregnant uterus were similar between genotypes. Ly49 KD lowered the normal frequencies of Ly49 1 uNK cells from 90.3% to 47.8% in DBA 2 DX5 1 and 78.8% to 6.3% in DBA 1 DX5 2 uNK cell subtypes. B6.Ly49 KD matings frequently resulted in expanded blastocysts that did not implant (subfertility). B6.Ly49 KD mice that established pregnancy had gestational lengths and litter sizes similar to controls. B6.Ly49 KD neonates, however, were heavier than controls. B6.Ly49 KD implantation sites lagged in early (gd6.5) decidual angiogenesis and were deficient in mid-pregnancy (gd10.5) spiral arterial remodelling. Ultrastructural analyses revealed that B6.Ly49 KD uNK cells had impaired granulogenesis, while immunocytochemistry revealed deficient vascular endothelial cell growth factor (VEGFA) production. Perforin and IFNG expression were normal in B6.Ly49 KD uNK cells. Thus, in normal mouse pregnancies, Ly49 receptor signaling must promote implantation, early decidual angiogenesis and mid-pregnancy vascular remodelling. Disturbances in these functions may underlie the reported genetic associations between human pregnancy complications and the inability of specific conceptus MHCs to engage activating KIR on uNK cells.

show abstract

Imaging of Vascular Development in Early Mouse Decidua and Its Association with Leukocytes and Trophoblasts1

Cited by 103 publications

References 52 publications

Unique Roles of Infiltrating Myeloid Cells in the Murine Uterus during Early to Midpregnancy

Unique Roles of Infiltrating Myeloid Cells in the Murine Uterus during Early to Midpregnancy

HLA-G-mediated NK cell senescence promotes vascular remodeling: implications for reproduction

Ly49 receptors activate angiogenic mouse DBA+ uterine natural killer cells

Contact Info

Product

Resources

About