Impacts of a perinatal exposure to manganese coupled with maternal stress in rats: Maternal somatic measures and the postnatal growth and development of rat offspring

Psychological stress experienced by the mother during pregnancy has been associated with emotional and cognitive disorders in children such as depression and anxiety. Socioeconomically disadvantaged populations are vulnerable to adverse life experiences and can also be disproportionally exposed to environmental contaminants. To better understand the neurodevelopmental impacts of an environmental toxicant coupled with elevated psychological stress, we exposed pregnant rats to a series of perinatal stressors. Manganese (Mn), a neurotoxicant at excessive concentrations was delivered through drinking water (0, 2, or 4 mg/mL) from gestational day (GD) 7 to postnatal day (PND) 22. A variable stress paradigm was applied to half of the animals from GD13 to PND9. Measurements of somatic development and behavior were examined in the offspring at different developmental stages. No evidence of overt maternal toxicity was observed although the 4 mg/mL Mn-exposed dams gained less body weight during gestation compared to the other dams. Stress also reduced gestational maternal weight gain. Daily fluid consumption normalized for body weight was decreased in the Mn-exposed dams in a dose-dependent manner but was not altered by the stress paradigm. Maternal stress and/or Mn exposure did not affect litter size or viability, but pup weight was significantly reduced in the 4 mg/mL Mn-exposed groups on PNDs 9 through 34 when compared to the other offspring groups. The efficacy of the manipulations to increase maternal stress levels was determined using serum corticosterone as a biomarker. The baseline concentration was established prior to treatment (GD7) and levels were low and similar in all treatment groups. Corticosterone levels were elevated in the perinatal-stress groups compared to the no-stress groups, regardless of Mn exposure, on subsequent time points (GD16, PND9), but were only significantly different on GD16. An analysis of tissue concentrations revealed Mn was elevated similarly in the brain and blood of offspring at PND2 and at PND22 in a significant dose-dependent pattern. Dams also showed a dose-dependent increase in Mn concentrations in the brain and blood; the addition of stress increased the Mn concentrations in the maternal blood but not the brain. Perinatal stress did not alter the effects of Mn on the maternal or offspring somatic endpoints described here.