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Progesterone improves perinatal neuromotor outcomes in a mouse model of intrauterine inflammation via immunomodulation of the placenta
Author(s) -
Novak Christopher M.,
Ozen Maide,
McLane Michael,
Alqutub Sadiq,
Lee Ji Yeon,
Lei Jun,
Burd Irina
Publication year - 2018
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/aji.12842
Subject(s) - offspring , fetus , medicine , placenta , lipopolysaccharide , neuroprotection , inflammation , andrology , pregnancy , umbilical cord , endocrinology , immunology , biology , genetics
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.