Identification of the primary outcomes that result from deficient spiral arterial modification in pregnant mice

Croy, B. Anne; Burke, Suzanne D.; Barrette, Valerie F.; Zhang, Jianhong; Hatta, Kota; Smith, Graeme N.; Bianco, Juares; Yamada, Áureo T.; Adams, Michael

doi:10.1016/j.preghy.2010.10.002

Cited by 37 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NK + T + B + ) and alymphoid (deficient in NK, T and B cells (NK − T − B − )) BALB/c-Rag2 −/− / Il2rg −/− mice before, across and after pregnancy using micro-ultrasound. Unlike most patients with impaired SA remodeling, 24 Rag2 −/− /Il2rg −/− dams with unmodified SA have normotensive pregnancies without detectable elevation in hypoxia of placental, fetal or maternal tissue. 25 They also show no elevation in fetal loss and their offspring are not growth impaired.…”

Section: Introductionmentioning

confidence: 88%

See 1 more Smart Citation

Alterations in maternal and fetal heart functions accompany failed spiral arterial remodeling in pregnant mice

Zhang

Adams

Croy

2011

American Journal of Obstetrics and Gynecology

Self Cite

View full text Add to dashboard Cite

OBJECTIVE-Our goal was to define mechanisms that protect murine pregnancies deficient in spiral arterial (SA) remodeling from hypertension, hypoxia and intra-uterine growth restriction.STUDY DESIGN-Micro-ultrasound analyses were conducted on virgin, gestation day (gd) 2,4,7,9,10,12,14,16,18 and postpartum BALB/c (WT) mice and BALB/c-Rag2 −/− /Il2rg −/− mice, an immunodeficient strain lacking SA remodeling. RESULTS-Rag2−/− /Il2rg −/− dams had normal SA flow velocities, greatly elevated uterine artery flow velocities between gd10-16 and smaller areas of placental flow from gd14 to term than controls. Maternal heart weight and output increased transiently. Conceptus alterations included higher flow velocities in the umbilical-placental circulation that became normal before term and bradycardia persistent to term.CONCLUSION-Transient changes in maternal heart weight and function accompanied by fetal circulatory changes successfully compensate for deficient SA modification in mice. Similar compensations in humans may contribute to post-partum pregnancy gains elevated risk of cardiovascular disease associated with preeclampsia.

show abstract

Section: Introductionmentioning

confidence: 88%

“…Mean litter sizes in this study were not significantly different between genotypes. 24 All procedures were conducted under Animal Utilization Protocols approved by the Animal Care Committee, Queen's University.…”

Section: Micementioning

confidence: 99%

Alterations in maternal and fetal heart functions accompany failed spiral arterial remodeling in pregnant mice

Zhang

Adams

Croy

2011

American Journal of Obstetrics and Gynecology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In one, blastocysts transduced with a lentiviral vector expressing hsFLT1 (an anti-angiogenic factor) the levels of hsFLT1 can be detected early in pregnancy, and gradually drive to late PE-like hypertensive and renal consequences. 6 Mouse spiral arterial remodeling is seen histologically over gestation days (gd) 10-12 of the 19-20 day pregnancy 5,7 and is a process that includes downregulation of arterial markers and acquisition of venous antigen expression. 8 Thus, spiral arterial remodeling is a mid-gestational event that coincides with the completion of placental and fetal differentiation/development and the onset of rapid fetal growth.…”

Section: Introductionmentioning

confidence: 99%

Leukocyte driven-decidual angiogenesis in early pregnancy

et al. 2014

Self Cite

View full text Add to dashboard Cite

Successful pregnancy and long-term, post-natal maternal and offspring cardiac, vascular and metabolic health require key maternal cardiovascular adaptations over gestation. Within the pregnant decidualizing uterus, coordinated vascular, immunological and stromal cell changes occur. Considerable attention has been given to the roles of uterine natural killer (uNK) cells in initiating decidual spiral arterial remodeling, a process normally completed by mid-gestation in mice and in humans. However, leukocyte roles in much earlier, region specific, decidual vascular remodeling are now being defined. Interest in immune cell-promoted vascular remodeling is driven by vascular aberrations that are reported in human gestational complications such as infertility, recurrent spontaneous abortion, preeclampsia (PE) and fetal growth restriction. Appropriate maternal cardiovascular responses during pregnancy protect mothers and their children from later cardiovascular disease risk elevation. One of the earliest uterine responses to pregnancy in species with hemochorial placentation is stromal cell decidualization, which creates unique niches for angiogenesis and leukocyte recruitment. In early decidua basalis, the aspect of the implantation site that will cradle the developing placenta and provide the major blood vessels to support mature placental functions, leukocytes are greatly enriched and display specialized properties. UNK cells, the most abundant leukocyte subset in early decidua basalis, have angiogenic abilities and are essential for normal early decidual angiogenesis. The regulation of uNK cells and their roles in determining maternal and progeny cardiovascular health over pregnancy and postpartum are discussed.

show abstract

“…[14][15][16] Recent findings, both in humans and mice, have shown that uterine NK cells are involved in endometrial remodeling, spiral artery modifications and placentation. [17][18][19][20][21] Although a large body of information on uterine NK cell function comes from data in mice, our knowledge regarding the presence and the phenotype of murine NK cells in decidua and uterus during early pregnancy (first week) is still incomplete. Another important question concerns their origin: they can be generated in situ from precursors or recruited from the periphery into decidua and uterus, where the microenvironment can modulate their phenotypic and functional characteristics.…”

Section: Introductionmentioning

confidence: 99%

In vivo generation of decidual natural killer cells from resident hematopoietic progenitors

et al. 2013

View full text Add to dashboard Cite

© F e r r a t a S t o r t i F o u n d a t i o nproperties of mature NK cells. Various markers allow the identification of different stages of NK cell maturation. The first to appear are NKG2D and NK1.1, followed by NKp46, CD94/NKG2A/C/E, CD27, DX5, Ly49 receptors and CD11b. 28,36 39 A recent report suggested that mouse uNK cells are heterogeneous and considering only DBA + uNK cells could bias information on the uNK cell population. 40 Since studies in humans clearly indicated that NK cells represent the most frequent lymphoid cell population during early pregnancy (first trimester), playing a fundamental role in the establishment and maintenance of pregnancy, it would be important to gain more information in mice. 12,18,41,42 In the present study, for the first time, murine NK cells were analyzed separately in decidua and uterus. We found that high proportions of immature NK cells are present both in decidua and uterus during the first week of pregnancy. In addition, we identified NK-committed hematopoietic precursors (Lin -CD122 + ) in decidua and uterus of pregnant mice. Transfer experiments of peripheral EGFP + -NK cells indicated that these cells are not recruited mainly into decidua and uterus, thus do not contribute to the accumulation of dNK and uNK cells during early pregnancy. In contrast, EGFP + -NKP transferred into pregnant mice rapidly migrated into decidua and uterus where they underwent proliferation and differentiation towards mature NK cells. Immature dNK and uNK display phenotypic and functional features similar to those previously described in humans. These data provide important information regarding the biology of NK cells in pregnancy, and identify novel tissues (decidua and uterus) able to sustain peripheral NK cell differentiation in vivo. MethodsC57BL/6 and RAG-2 -/-mice were purchased from Charles River. Transplant donors were EGFP+ transgenic mice ((C57BL/6-Tg(ACTB-EGFP)1 Osb/J mice 5 (GFP-Tg)). Cells derived from spleen, decidua, uterus and BM were incubated with different mAbs and run on a flow cytometer. EGFP + NK cells and NKP were injected intravenously into unirradiated wild-type syngeneic mice at gestational day (gd) 0,5. The presence and the phenotype of the transferred EGFP + cells were analyzed in the different tissues at gd 3,5-5,5-7,5 by flow cytometry. Mice were given one i.p. injection of 1 mg of 5-bromo-2'-deoxyuridine (BrdU). After 18 h, mice were sacrificed and organs were analyzed. Frozen sections of pregnant uteri were stained with anti-NKp46 (R & D Systems, Minneapolis, MN, USA) and anti-Ki-67 (Abcam, Cambridge, UK) followed by Alexa 594 chicken anti-goat and Alexa 488 goat anti-rabbit (Life Technologies, CA, USA). The nuclei were counterstained with DAPI. Cells derived from decidua, uterus and spleen of pregnant mice at gd 5.5 were stimulated during 4 h-culture with the different antibodies, or with YAC-1 mouse lymphoma cells (effector/target ratio 1:1), or with a combination of phorbol myristate acetate (PMA) and ionomycin (IONO). Cells were analyzed by ...

show abstract

Identification of the primary outcomes that result from deficient spiral arterial modification in pregnant mice

Cited by 37 publications

References 41 publications

Alterations in maternal and fetal heart functions accompany failed spiral arterial remodeling in pregnant mice

Alterations in maternal and fetal heart functions accompany failed spiral arterial remodeling in pregnant mice

Leukocyte driven-decidual angiogenesis in early pregnancy

In vivo generation of decidual natural killer cells from resident hematopoietic progenitors

Contact Info

Product

Resources

About