Effects of Prenatal Stress, Prenatal Diet, and Maternal Genotype on Autistic-Like Behavior in Mice
“Background: Multiple studies have reported prenatal stress as a potential risk factor for the development of autism spectrum disorder (ASD). In rodents, a significant reduction in sociability is seen in prenatally stressed offspring of serotonin transporter knockout heterozygous (5-HTT +/-) dams. Additionally, offspring with prenatal maternal diets rich in omega-6 polyunsaturated fatty acids (PUFAs) show decreased social interactions. Finally, diets rich in omega-3 PUFAs are thought to be neuroprotective and may reduce the impact of factors such as the aforementioned gene-stress interaction.
Objectives: In our study, we examined the effects of prenatal diet, prenatal stress, and maternal genotype on behavior in offspring mice.
Methods: Pregnant C57BL/6J and 5-HTT +/- dams were subjected to either chronic variable stress or no stress, with each group further divided into receiving one of four diets beginning 2 weeks before breeding and lasting until offspring were weaned: AIN-93G, AIN-93G with added safflower oil, AIN-93G with added flaxseed oil, and AIN-93G with added pure DHA. Chronic variable stressed mice were given one stressor per day beginning on gestational day 6 until the birth of the offspring. We subsequently recorded the ultrasonic vocalizations (USVs) of the offspring on postnatal day (PD) 8 as a measure of social communication. Beginning on PD 60, adult offspring were tested for sociability, anxiety, and locomotor functioning using a 3-chambered social approach task, an elevated-plus maze, an open field and a rotarod task.
Results: Prenatally stressed offspring of 5-HTT +/- dams displayed a decrease in USVs compared to WT control offspring. Additionally, a diet rich in omega-6 PUFAs decreased the amount of USVs in non-stressed offspring of WT dams. Prenatally stressed offspring of SERT +/- dams exposed to the omega-3 PUFA rich diet had a similar number of calls to those exposed to the control diet. Results are forthcoming in the 3-chambered social approach task, elevated-plus maze, open field and rotarod task, as data has been collected and is currently being analyzed. We expect a decrease in sociability as well as an increase in anxiety in prenatally stressed 5-HTT +/- offspring as well as in offspring exposed to the AIN-93G with added safflower oil prenatal diet. Finally, we expect prenatally stressed 5-HTT +/- offspring exposed to the AIN-93G with added pure DHA diets to display normal sociability and anxiety levels.
Conclusions: This study provides evidence for a role of maternal genotype, prenatal stress and prenatal diet in offspring sociability in a potential animal model of ASD. Exploration of the relationship between maternal genotype, prenatal stress, prenatal diet and ASD in humans will be necessary to determine the role of this finding in clinical ASD, and further investigation into the mechanism of action of this effect is warranted.”