Prenatal and lactational nitrate exposure in drinking water induces modest alterations in offspring sensorimotor development, physiology and adult locomotor activity in a rat model.

Nitrate (NO3-) is a common drinking water contaminant with a poorly characterised safety profile in pregnancy and early life. This study aimed to investigate whether guideline-level exposure to nitrate in drinking water throughout pre-conception, gestation and lactation influences offspring sensorimotor development, physiology and selected behavioural outcomes. Wistar rats were exposed to 0, 50 or 100mg/L NO3- as sodium nitrate in drinking water (n=6-7/group) three weeks pre-conception and throughout gestation and lactation. At 7-14 days of age, both groups of nitrate-exposed offspring had advanced sensorimotor development in negative geotaxis testing compared to controls. At weaning, maternal plasma nitrate and nitrite were significantly increased in the nitrate exposed groups, offspring plasma nitrate increased modestly, while offspring plasma nitrite did not increase. Further, at this timepoint, offspring corticosterone concentrations and female offspring kidney weight were increased in the 100mg/L group. The clinical significance of these differences is unclear, and they were not apparent in later life. Elevated plus maze and object recognition tests revealed no memory deficits or anxiety-like phenotype, although male offspring exposed to 100mg/L NO3- consistently displayed reduced locomotor activity. Human research on the neurodevelopmental effects of moderate early-life nitrate exposure through drinking water is limited and the exact mechanism/s through which nitrate impacts physiology and behaviour remains elusive. This study highlights the need to prioritise further investigation in these areas and raises concern for the appropriateness of current nitrate guidelines given the lower sensitivity of rats to nitrate than humans.