In vivo assessment of the placental anatomy and perfusion in a mouse model of intrauterine inflammation

Wu, Dan; Lei, Jun; Jia, Bei; Xie, Han; Zhu, Yan; Xu, Jiadi; Mori, Susumu; Zhang, Jiangyang; Burd, Irina

doi:10.1002/jmri.25867

Cited by 10 publications

(11 citation statements)

References 38 publications

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“…We speculate that these effects may contribute to the formation of a clot, subsequently decreasing placental volume. The results of our current study add further support to this speculation and correlate the acute placental injury following IUI to fetal sequelae [45].…”

Section: Discussionsupporting

confidence: 81%

“…Our study is supported by our prior work investigating MRI-based placental perfusion deficits following the exposure to IUI [44]. Specifically, we used MRI to examine placental damage following IUI and found a significant decrease in capillary blood volume and velocity, suggestive of vascular damage and blood flow disruption [44,45,46]. We speculate that these effects may contribute to the formation of a clot, subsequently decreasing placental volume.…”

Section: Discussionsupporting

confidence: 78%

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Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae

Eloundou

Lee

et al. 2019

PLoS ONE

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Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury. CD1 pregnant dams underwent laparotomies and received intrauterine injections of either lipopolysaccharide (LPS; a model of IUI) or phosphate-buffered saline (PBS). In utero ultrasound Doppler velocimetry of uterine and umbilical arteries and magnetic resonance imaging (MRI) of placental volumes with confirmatory immunohistochemical (vimentin) and histochemistry (fibrin) analyses were performed. ELISA for thrombosis markers, fibrinogen and fibrin was performed to analyze thrombi in placenta. Fetal brain immunohistochemistry was performed to detect microglial activation (ionized calcium-binding adaptor molecule 1, Iba1). On ultrasound, LPS group demonstrated elevated resistance indices, pulsatility indices and a greater occurrence of absent end-diastolic flow in the umbilical and uterine arteries. In the fetus, there was an increased cardiac Tei indices in the LPS group. MRI revealed decreased volume of placenta in the LPS group associated with placental thinning and placental endothelial damage on immunohistochemistry. Decreased fibrinogen content and more thrombi staining in placenta exposed to maternal LPS indicated the hypercoagulability. Furthermore, the expression of Iba1was significantly associated with placental thickness (r = -0.7890, Pearson correlation coefficient). Our data indicate that IUI can trigger events leading to maternal placental malperfusion and fetal vessel resistance, as well as predispose the developing fetus to cardiac dysfunction and brain damage. Furthermore, our data suggest that prenatal ultrasound can be a real-time clinical tool for assessing fetal risk for adverse neurologic outcomes following the potential IUI exposure.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 78%

Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae

Eloundou

Lee

et al. 2019

PLoS ONE

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“…LPS itself has been shown to induce hypoglycemia (Tweedell et al., 2011; Yanay, Bailey, Kernan, Zimmerman, & Osborne, 2015). Wu et al (2018) reported that after intrauterine injection of LPS, magnetic resonance imaging (MRI) showed significantly decreased placental perfusion, and the placental capability in response to maternal glucose challenge was impaired. These studies indicate that LPS‐induced IUI may affect the energy substrate intake of the fetal brain and lead to abnormal neuron cells growth and metabolism.…”

Section: Discussionmentioning

confidence: 93%

“…It is possible that, at this time point, the inhibited mTOR activity in LPS fetal brains is linked with insufficient energy supply from mother to fetus. Wu et al (2018) observed that at 6 hr after intrauterine injection of LPS, MRI showed significantly decreased placental perfusion, suggesting the LPS fetal brains may not be obtaining enough nutrients. Subsequently, after 24 hr of LPS exposure, mTOR signaling displays an overall inhibition in LPS fetal brains based on the low expression of p‐mTOR, p‐4Ebp1, p‐S6k, and p‐rpS6.…”

Section: Discussionmentioning

confidence: 99%

The effect of intrauterine inflammation on mTOR signaling in mouse fetal brain

Dong

Lei

Elsayed

et al. 2020

Developmental Neurobiology

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Fetuses exposed to an inflammatory environment are predisposed to long‐term adverse neurological outcomes. However, the mechanism by which intrauterine inflammation (IUI) is responsible for abnormal fetal brain development is not fully understood. The mechanistic target of rapamycin (mTOR) signaling pathway is closely associated with fetal brain development. We hypothesized that mTOR signaling might be involved in fetal brain injury and malformation when fetuses are exposed to the IUI environment. A well‐established IUI model was utilized by intrauterine injection of lipopolysaccharide (LPS) to explore the effect of IUI on mTOR signaling in mouse fetal brains. We found that microglia activation in LPS fetal brains was increased, as demonstrated by elevated Iba‐1 protein level and immunofluorescence density. LPS fetal brains also showed reduced neuronal cell counts, decreased cell proliferation demonstrated by low Ki67‐positive density, and elevated neuron apoptosis evidenced by high expression of cleaved Caspase 3. Furthermore, we found that mTOR signaling in LPS fetal brains was elevated at 2 hr after LPS treatment, declined at 6 hr and showed overall inhibition at 24 hr. In summary, our study revealed that LPS‐induced IUI leads to increased activation of microglia cells, neuronal damage, and dynamic alterations in mTOR signaling in the mouse fetal brain. Our findings indicate that abnormal changes in mTOR signaling may underlie the development of future neurological complications in offspring exposed to prenatal IUI.

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“…This model mimics the most common clinical scenario associated with preterm birth. In this model, we have previously identified acute maternal vascular malperfusion (MVM) with IVIM and immunohistochemistry measurements in the placenta [47], and thus, the model serves as an ideal test bed for potential clinical translation of DGE MRI to assess placental function. In this study, we performed DGE MRI to examine the time-resolved placental response to a glucose challenge in LPS- exposed placentae, in comparison with the controls.…”

Section: Introductionmentioning

confidence: 99%

Dynamic glucose enhanced MRI of the placenta in a mouse model of intrauterine inflammation

Lei

et al. 2018

Placenta

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In vivo assessment of the placental anatomy and perfusion in a mouse model of intrauterine inflammation

Abstract: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1260-1267.

Cited by 10 publications

References 38 publications

Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae

Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae

The effect of intrauterine inflammation on mTOR signaling in mouse fetal brain

Dynamic glucose enhanced MRI of the placenta in a mouse model of intrauterine inflammation

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