Maternal separation stress experienced by parents affects ovarian function in first generation of mice

The maternal separation stress during postnatal development can adversely affect one’s adulthood. Some parents’ experiences may not only affect the phenotype of parents but also alter the reaction to environmental impacts in the offspring. The aim of this study is to investigate consequences of maternal separation stress in female first generation of mice whose parents were exposed to maternal separation stress. Maternal separation in pups was performed during post-natal days (PND) 2 to 14. Then, female pups of the first-generation were used in present study. The histological changes in ovaries, ROS production (using DCFH-DA assay), mRNA expression of NLRP3, ASC, caspase-1, TLR4, BAX, BCL2 and TNFα genes (using RT-PCR), levels of IL-18, IL-1β, ATP and GPx (using ELISA) and also protein expression of caspase-3 and NLRP3 (using immunocytochemistry) were assessed. Our findings showed that maternal separation stress experienced by parents significantly affects the numbers of primordial and primary follicles. Furthermore, ROS production increased and concentrations of ATP and GPx reduced in the first generation. Also, expression of cytokines and genes involved in inflammation and apoptosis including NLRP3, caspase-1, TLR4, TNFα, IL-1β, IL-18 and BCL2 were significantly affected in the first generation. Our results also showed that this stress significantly increased percentage of caspase-3 and NLRP3 positive cells in the ovarian tissue of the first generation. Our findings suggest that maternal separation stress experienced by parents may influence activation of inflammatory response in the ovarian tissue of their first generation which may induce apoptosis and consequently disturb folliculogenesis process.