Adapting an organ‐on‐chip device to study the effect of fetal sex and maternal race/ethnicity on preterm birth related intraamniotic inflammation leading to fetal neuroinflammation

Autor: Lauren S. Richardson, Nkechinyere Emezienna, Irina Burd, Brandie D. Taylor, Morgan R. Peltier, Arum Han, Ramkumar Menon
Rok vydání: 2022
Předmět:
Zdroj: American Journal of Reproductive Immunology. 88
ISSN: 1600-0897
1046-7408
Popis: Fetal neuroinflammation has been linked to preterm birth-related intraamniotic infection and inflammation; However, the contribution of fetal sex and maternal race/ethnicity is unknown. To determine if fetal sex and maternal race/ethnicity influence neuroinflammation, an organ-on-chip (OOC) model were established under normal or pathologic conditions utilizing amniotic fluid.OOC is composed of two-cell culture chambers connected by Type IV collagen-coated microchannels. Human fetal astroglia (SVGp12) and microglia (HMC3) were co-cultured at an 80:20 ratio in the inner chamber. The outer chamber contained amniotic fluid (AF) from male and female fetuses of White Hispanic (WH) and African-American (AA) pregnant women with or without lipopolysaccharide (LPS-100 ng/ml) and incubated for 48 h. Glial migration (brightfield microscopy), activation (Immunocytochemistry), and cytokine production (Luminex assays) were quantified and compared (N = 4 for each category of sex and race/ethnicity).In a pooled analysis, AF+LPS did not induce glial activation or inflammatory changes compared to AF alone. When stratified by sex, male AF+LPS promoted significant glial activation (high CD11b:p 0.05; low Iba1:p 0.01) compared to male AF without LPS; however, this was not associated with changes in pro-inflammatory cytokines. When stratified by race/ethnicity, AF+LPS induced glial activation in both groups, but a differential increase in pro-inflammatory cytokines was seen between WH and AA AF (WH-interleukin-1β: p 0.05; AA-interleukin-8: p 0.01).This OOC model of fetal neuroinflammation has determined that race/ethnicity differences do exist for perinatal brain injury. The fetal sex of neonates was not a determining factor of susceptibility to intraamniotic inflammation leading to neuroinflammation.
Databáze: OpenAIRE
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