Fetal and maternal inflammatory response in the setting of maternal intrapartum fever with and without clinical and histologic chorioamnionitis

Lagodka, Sylvie; Petrucci, Samantha; Mortti, Michael L; Cabbad, Michael; Lakhi, Nisha

doi:10.1016/j.ajogmf.2021.100539

Cited by 7 publications

(4 citation statements)

References 24 publications

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“…All microglial substates displayed high, sustained expression of receptors for cytokines known to be involved in the response to MIA, including Il17ra and Il6ra . All microglial substates also highly expressed receptors for a subset of cytokines involved in maternal fever, including IL-6, IL-8, and interferon-gamma 56,57 . These receptor patterns suggest that microglia, as compared to most other cell types in the dorsal cortex, are more poised to respond to MIA and systemic inflammatory stimuli during fetal development.…”

Section: Resultsmentioning

confidence: 99%

Fetal brain response to maternal inflammation requires microglia

Elaine LaMonica Ostrem,

Dominguez Iturza,

Stogsdill

et al. 2024

Preprint

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In uteroinfection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal central nervous system infection, is associated with an increased risk of autism and schizophrenia in affected offspring. The cell types mediating the response of the fetal brain to maternal inflammation are largely unknown, hindering the development of therapies to prevent and treat adverse neuropsychiatric outcomes. Here, we show that microglia, the resident phagocytes of the brain, are enriched for expression of receptors for relevant pathogens and cytokines, throughout embryonic development. Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant dams, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life. We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA. These findings demonstrate that microglia play a critical, durable role in fetal response to maternal inflammation, pointing at microglia as a potential therapeutic cell target.

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Section: Resultsmentioning

confidence: 99%

Fetal brain response to maternal inflammation requires microglia

Elaine LaMonica Ostrem,

Dominguez Iturza,

Stogsdill

et al. 2024

Preprint

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show abstract

“…All microglial substates displayed high and sustained expression of receptors for cytokines known to be involved in the response to MIA, including Il17ra and Il6ra . All microglial substates also highly expressed receptors for a subset of cytokines involved in maternal fever, including IL-6, IL-8 and interferon gamma ( Romero et al, 2016 ; Lagodka et al, 2022 ). These receptor patterns suggest that microglia, when compared with most other cell types in the dorsal cortex, are more poised to respond to MIA and systemic inflammatory stimuli during fetal development.…”

Section: Resultsmentioning

confidence: 99%

Fetal brain response to maternal inflammation requires microglia

LaMonica Ostrem,

Domínguez-Iturza,

Stogsdill

et al. 2024

Development

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In utero infection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. The cell types mediating the fetal brain response to maternal inflammation are largely unknown, hindering the development of novel treatment strategies. Here, we show that microglia, the resident phagocytes of the brain, highly express receptors for relevant pathogens and cytokines throughout embryonic development. Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life. We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA. These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets.

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“…This relationship between chorioamnionitis and IL-1 abundance in cord blood is less clear. Increased IL-1β was associated with chorioamnionitis in a select number of studies (75)(76)(77), however other studies reported no difference (78)(79)(80)(81). This discrepancy may be explained by the concurrent presence of funisitis, an indicator of the fetal inflammatory response, marked by focal aggregation of polymorphonuclear leukocytes at the umbilical cord surface (77).…”

Section: Clinical Association Of Il-1 In Maternal and Fetal Chorioamn...mentioning

confidence: 98%

“…IL1B mRNA expression is increased in maternal serum (74) during chorioamnionitis. Conflicting evidence: reports of increased IL-1 in cord blood from chorioamnionitisaffected pregnancies (75)(76)(77) however not in all studies (78)(79)(80)(81). May require concurrent funisitis (77).…”

Section: Chorioamnionitismentioning

confidence: 99%

The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation

Owen

Garrick²,

Peterson³

et al. 2023

Front. Pediatr.

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Preterm birth is defined as delivery at <37 weeks of gestational age (GA) and exposes 15 million infants worldwide to serious early life diseases. Lowering the age of viability to 22 weeks GA entailed provision of intensive care to a greater number of extremely premature infants. Moreover, improved survival, especially at extremes of prematurity, comes with a rising incidence of early life diseases with short- and long-term sequelae. The transition from fetal to neonatal circulation is a substantial and complex physiologic adaptation, which normally happens rapidly and in an orderly sequence. Maternal chorioamnionitis or fetal growth restriction (FGR) are two common causes of preterm birth that are associated with impaired circulatory transition. Among many cytokines contributing to the pathogenesis of chorioamnionitis-related perinatal inflammatory diseases, the potent pro-inflammatory interleukin (IL)-1 has been shown to play a central role. The effects of utero-placental insufficiency-related FGR and in-utero hypoxia may also be mediated, in part, via the inflammatory cascade. In preclinical studies, blocking such inflammation, early and effectively, holds great promise for improving the transition of circulation. In this mini-review, we outline the mechanistic pathways leading to abnormalities in transitional circulation in chorioamnionitis and FGR. In addition, we explore the therapeutic potential of targeting IL-1 and its influence on perinatal transition in the context of chorioamnionitis and FGR.

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Fetal and maternal inflammatory response in the setting of maternal intrapartum fever with and without clinical and histologic chorioamnionitis

Cited by 7 publications

References 24 publications

Fetal brain response to maternal inflammation requires microglia

Fetal brain response to maternal inflammation requires microglia

Fetal brain response to maternal inflammation requires microglia

The role of interleukin-1 in perinatal inflammation and its impact on transitional circulation

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