Effects of multiple pro-inflammatory stimuli

Area of Science:

• Perinatal medicine
• Developmental biology
• Gastroenterology

Background:

• Chorioamnionitis is a frequent complication of preterm birth.
• It is linked to increased risks of intestinal inflammation and necrotizing enterocolitis in neonates.
• Intestinal inflammation can disrupt the development of the enteric nervous system.

Purpose of the Study:

• To investigate the effects of chorioamnionitis, induced by Ureaplasma parvum and/or lipopolysaccharide (LPS), on fetal ileal inflammation and enteric nervous system (ENS) development.
• To determine if repeated or chronic exposure to inflammatory stimuli impacts these outcomes.
• To model early-life inflammation at a gestational age equivalent to 60% of term.

Main Methods:

• Ovine fetuses were exposed to chronic Ureaplasma parvum and/or LPS via intra-amniotic injections at varying durations before delivery.
• Intestinal inflammation was assessed by quantifying inflammatory cell markers (CD3, myeloperoxidase).
• ENS structural changes were evaluated by assessing neuronal nuclei and glial cell (astrocyte-like) populations.

Main Results:

• LPS exposure increased inflammatory cell infiltration.
• Repetitive LPS or combined Ureaplasma parvum/LPS exposure significantly elevated intestinal inflammation.
• Neuronal cell nuclei decreased across all intervention groups, most notably with repetitive LPS.
• Astrocyte-like glial cells increased following LPS exposure (2 days prior) or chronic Ureaplasma parvum exposure.

Conclusions:

• Exposure to chorioamnionitis in fetal development leads to significant intestinal inflammation and structural alterations in the ENS.
• The severity of these inflammatory and structural changes is dose- and duration-dependent.
• These findings highlight potential long-term functional consequences for infants exposed to prenatal inflammation.