Abstract
Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organs
Highlights
Adverse perinatal outcomes include both prematurity and/or low birthweight
While mechanisms of tolerance between mother and fetus are not completely understood, it is clear that dendritic cells (DCs), T cells and natural killerd (NK) cells play crucial roles at the maternal-fetal interface and in maternal tissues to ensure that pregnancy proceeds successfully [15]
An important feature of our model of adverse perinatal outcome model is that localized cystitis induced delayed infiltration of Polymorphonuclear neutrophils (PMNs) and macrophages in distal organs
Summary
Adverse perinatal outcomes include both prematurity (birth prior to 37 weeks) and/or low birthweight (weight below 2500 grams). Premature and low birthweight neonates have increased rates of morbidity and mortality in the first year of life and suffer from a plethora of life-long health conditions including: neurological, respiratory, gastrointestinal, cardiovascular, and immunological [12,13]. These health conditions are more severe when the mother experiences infections during pregnancy [14]. While the immune system normally functions to attack non-self stimuli, successful gestation requires the maternal immune response to ‘‘ignore’’ paternal antigens produced by the fetus (termed: fetal tolerance). Th2/3 cells prevent maternal immune responses from attacking the developing outbred fetus to maintain healthy pregnancies [15]
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