Progesterone improves perinatal neuromotor outcomes in a mouse model of intrauterine inflammation via immunomodulation of the placenta

To assess the fetal neuroprotective potential of progesterone using a well‐validated mouse model of lipopolysaccharide ( LPS )‐induced intrauterine inflammation ( IUI ). Embryonic day 17 pregnant mouse dams (n = 69) were randomly allocated to receive 17‐hydroxyprogesterone caproate (17‐ OHPC ), micronized progesterone ( MP ), or vehicle 1 hour prior to intrauterine injection of phosphate‐buffered saline ( PBS ) or LPS . After 6 hours, mice were killed for the collection of placentas and fetal brains, or pregnancy continued for the evaluation of preterm birth ( PTB ) and offspring neuromotor function. Placentas and fetal brains were analyzed by mini‐ mRNA array for 96 immune markers with individual confirmatory qPCR . Progesterone pre‐treatment before LPS ‐induced IUI improved neuromotor tests in offspring at PND 5 compared to no pre‐treatment ( P  <   .05). In placentas, 17‐ OHPC , but not MP , significantly reduced CXCL 9 ( P  <   .05) with a trend toward a lower level of CXCL 10. In fetal brains, 17‐ OHPC significantly reduced CXCL 9 compared to no pre‐treatment ( P  <   .05) and IL ‐1β compared to pre‐treatment with MP ( P  <   .01). Progesterone pre‐treatment prior to LPS ‐induced IUI improved offspring neuromotor outcomes. 17‐ OHPC , but not MP , resulted in greater immunomodulation of T cell‐mediated immunity in placenta and fetal brain, suggesting a possible mechanism for the observed neuroprotective effects.