Prenatal Stress Leads to Intrauterine Dysfunction and Offspring Behavioral Deficits

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Prenatal stress (PNS) is associated with neuropsychiatric disorders in offspring, including anxiety, depression, and autism. There is mounting evidence that these behavioral phenotypes have origins in utero. Maternal microbes and inflammation have been implicated as potential mediators of the behavioral consequences of PNS; whether and how these systems interact is unclear. Here, we examine the effects of PNS in utero using late-gestation maternal restraint stress in wild-type (WT), germ-free (GF), and CCL2-/- genetic knock-out (KO) mice. In WT mice, PNS leads to placental and fetal brain inflammation, including an elevation in the chemokine CCL2. This inflammation is largely absent in GF mice, indicating the critical role of maternal microbes in mediating immune processes in utero. Furthermore, PNS in the absence of CCL2 failed to increase pro-inflammatory cytokine IL-6 in the fetal brain. PNS induced a pro-inflammatory phenotype in fetal microglia, which may be the source of the CCL2- and microbe-dependent inflammation in the fetal brain. Finally, PNS offspring exhibited deficits in sociability and anxiety-like behavior that were absent in CCL2-/- PNS offspring. Altogether, these findings suggest that a complex interaction between maternal microbes and inflammation regulates the emergence of behavioral abnormalities following PNS.


Health Sciences: 3rd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)


prenatal stress, microbes, CCL2, microglia, social behavior, placenta