Behavioral, genetic and biochemical changes in the brain of the offspring of female mice treated with caffeine during pregnancy and lactation

The intrauterine environment is a critical location for exposure to exogenous and endogenous factors that trigger metabolic changes through fetal programming. Among the external factors, chemical compounds stand out, which include caffeine, since its consumption is common among women, including during pregnancy. Thereby, the aim of the present study was to evaluate the behavioral, genetic, and biochemical parameters in the offspring of female mice treated with caffeine during pregnancy and lactation. Swiss female mice (60 days old) received tap water or caffeine at 0.3 or 1.0 mg/mL during copulation (7 days), pregnancy (21 days) and lactation (21 days). After the end of the lactation period, the offspring were divided into groups (water, caffeine 0.3 or 1.0 mg/ mL) with 20 animals (10 animals aged 30 days and 10 animals aged 60 days per group per sex). Initially, the offspring were submitted to behavioral tasks and then euthanized for genetic and biochemical analysis in the brain (cortex, striatum, and hippocampus). Behavioral changes in memory, depression, and anxiety were observed in the offspring: 30-day-old female offspring at 1.0 mg /mL dose presented anxiogenic behavior and male offspring the 0.3 mg/mL dose at 30 days of age did not alter long-term memory. Furthermore, an increase in DNA damage and oxidative stress in the brain were observed in the offspring of both sexes. Furthermore, there were changes in Ape-1, BAX, and Bcl-2 in the female offspring hippocampus at 30 days of life. Thus, with this study, we can suggest genotoxicity, oxidative stress, and behavioral changes caused by caffeine during pregnancy and lactation in the offspring that were not treated directly, but received through their mothers; thus, it is important to raise awareness regarding caffeine consumption among pregnant and lactating females.