Increased fetal cell trafficking in murine lung following complete pregnancy loss from exposure to lipopolysaccharide

Johnson, Kirby L.; Tao, Kai; Stroh, Helene; Kallenbach, Lisa R.; Peter, Inga; Richey, Lauren; Rust, Daniel W.; Bianchi, Diana W.

doi:10.1016/j.fertnstert.2009.08.042

Cited by 19 publications

(12 citation statements)

References 21 publications

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“…Mice were housed in standard cages with food and water ad libitum under a controlled environment (temperature = 20°C; humidity = 60%) and a light/dark cycle of 12 hr. Ts1Cje males (on a C57Bl/6J background) were crossed with C57Bl/6J females (Jackson Laboratories, Bar Harbor, ME) and the presence of a vaginal plug was defined as embryonic day 0.5 (E0.5) and 10% weight gain at embryonic day 10 as described previously [Johnson et al, 2010]. Pregnant females were anesthetized with 2.5% isoflurane in a 3/7 0 2 /N 2 O mixture and euthanized by decapitation at embryonic day E15.5 (E15.5).…”

Section: Methodsmentioning

confidence: 99%

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome

Guedj

Pennings

Ferres

et al. 2015

American J of Med Genetics Pt A

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Human fetuses with Down syndrome demonstrate abnormal brain growth and reduced neurogenesis. Despite the prenatal onset of the phenotype, most therapeutic trials have been conducted in adults. Here, we present evidence for fetal brain molecular and neonatal behavioral alterations in the Ts1Cje mouse model of Down syndrome. Embryonic day 15.5 brain hemisphere RNA from Ts1Cje embryos (n = 5) and wild type littermates (n = 5) was processed and hybridized to mouse gene 1.0 ST arrays. Bioinformatic analyses were implemented to identify differential gene and pathway regulation during Ts1Cje fetal brain development. In separate experiments, the Fox scale, ultrasonic vocalization and homing tests were used to investigate behavioral deficits in Ts1Cje pups (n = 29) versus WT littermates (n = 64) at postnatal days 3–21. Ts1Cje fetal brains displayed more differentially regulated genes (n = 71) than adult (n = 31) when compared to their age-matched euploid brains. Ts1Cje embryonic brains showed up-regulation of cell cycle markers and down-regulation of the solute-carrier amino acid transporters. Several cellular processes were dysregulated at both stages, including apoptosis, inflammation, Jak/Stat signaling, G-protein signaling, and oxidoreductase activity. In addition, early behavioral deficits in surface righting, cliff aversion, negative geotaxis, forelimb grasp, ultrasonic vocalization, and the homing tests were observed. The Ts1Cje mouse model exhibits abnormal gene expression during fetal brain development, and significant neonatal behavioral deficits in the pre-weaning period. In combination with human studies, this suggests that the Down syndrome phenotype manifests prenatally and provides a rationale for prenatal therapy to improve perinatal brain development and post-natal neurocognition.

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Section: Methodsmentioning

confidence: 99%

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome

Guedj

Pennings

Ferres

et al. 2015

American J of Med Genetics Pt A

Self Cite

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“…Alternatively, it is possible that the lungs (e.g. capillary endothelium) present a receptive microenvironment for retention and engraftment of these cells, or that homing to the lungs is stimulated by an as yet undetermined chemical axis [45], such as SDF-1/CXCR4, which promotes retention of a variety of cells in tissues.…”

Section: Pregnancy Associated Progenitor Cells (Papcs)mentioning

confidence: 99%

Pregnancy-associated progenitor cells: An under-recognized potential source of stem cells in maternal lung

et al. 2011

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Novel therapies are needed for the treatment of acute and chronic lung diseases, many of which are incurable. The use of exogenous stem cells has shown promise in both animal models and clinical trials. However, to date, the stem cell literature has under-recognized naturally acquired pregnancy-associated progenitor cells (PAPCs). These cells are found at sites of injury or disease in female tissues. They persist for decades after parturition in maternal blood and organs, with the largest number being found in the maternal lungs. Their presence there may be one explanation for the sex differences observed in the prevalence and prognosis of some lung diseases. Although the clinical significance of these cells is as yet unknown, the literature suggests that some of the PAPCs are stem cells or have stem cell-like properties. PAPCs harvested from the blood or organs of parous women could potentially be used as an alternate source of cells with regenerative properties for the woman herself or her children. Because PAPCs preferentially traffic to the maternal lung they may play a significant role in recovery or protection from lung disease. In this review article, we discuss ongoing research investigating the administration of both adult and placenta-derived stem cells to treat lung disease, and how PAPCs may also play an important future therapeutic role.

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“…An understanding of how hypoxic stress causes lineage imbalance early during mTSC differentiation in a mouse model should produce an understanding of the types of adaptive responses can also lead to maladaptive pathologies. Mouse models associated with spontaneous miscarriage 48, 49 , preeclampsia 50, 51 , intrauterine growth retardation 52 , and preterm labor have been produced and 80% of genes causing placental phenotypes in mouse are expressed in human placentation 53 . Thus the understanding of response of mTSCs induced by hypoxia <2% O 2 should provide insight into early placental pathology in humans.…”

Section: Introductionmentioning

confidence: 99%

Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

et al. 2014

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Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC), elevated O2 and mitochondrial function are necessary to placental lineages at the maternal-placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. Implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor (FGF)4 enabled highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2) initiated the most TSC differentiation after 24 hr despite FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential, maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos), and high pyruvate kinase M2 (glycolysis) despite FGF4 removal. Inhibiting OxPhos inhibited differentiation at the differentiation optimum at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2>0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

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Increased fetal cell trafficking in murine lung following complete pregnancy loss from exposure to lipopolysaccharide

Cited by 19 publications

References 21 publications

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome

The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome

Pregnancy-associated progenitor cells: An under-recognized potential source of stem cells in maternal lung

Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

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