The effects of oral gavage exposure during pregnancy and lactation on neonatal development in rat offspring

K McDonnell-Dowling1,2, S Kleefeld1,2, I Castro1,2, J P Kelly1,2. 1Discipline of Pharmacology and Therapeutics, NUI, Galway, Galway, Ireland, 2Galway Neuroscience Centre, National Centre for Biomedical Engineering Science, NUI, Galway, Galway, Ireland

In recent years, there has been an increase in the number of preclinical studies investigating prenatal and postnatal drug exposure. For such studies it is important to represent the human scenario and due to this oral gavage as a route of administration has been employed in order to mimic human exposure. The aim of this study was to determine if the restraint associated with oral gavage exposure during pregnancy and lactation can affect neurodevelopment in the rat offspring.

Pregnant Sprague-Dawley dams (n=10 dams/group) received distilled water via oral gavage (VEH) or no treatment (NT) daily from gestation day 7-21 and postnatal day (PND) 1-21. A range of well-recognised neurodevelopment parameters were examined in the offspring. Data were analysed using Repeated-Measures ANOVA and Two-way ANOVA or Friedman’s ANOVA and Mann-Whitney with relevant post-hoc tests. The level of significance was p<0.05.

VEH exposure had no effect on daily maternal body weight, food or water consumption during gestation or lactation. There was no significant difference in the number of pups born or sex ratios within the VEH-exposed litters compared to the NT litters. There was also no difference on the gestation length or incidence of stillborn and filial cannibalism. Somatic development (e.g. pinna unfolding, eye opening) was not affected by VEH-exposure however, behavioural development was altered in the VEH-exposed pups, in that more pups could perform surface righting but less pups could perform the forelimb grip compared to NT pups (Table 1).

Table 1: Neonatal developmental parameters. Data expressed as percentage of pups achieving the endpoint. ***p<0.001.

This study demonstrates that restraint handling during pregnancy does not have an effect on maternal outcome or pup somatic development. However, pup behavioural development seems to be enhanced in the early neonatal period but is poorer later into the neonatal period. Although both positive and negative results have been shown overall, these results do not raise any major concerns about oral gavage treatment resulting in impaired development in the rat offspring.