Maternal separation can affect the reproductive system by inflammasome activation in female mice

Objective The aim of this study is to investigate effect of maternal separation stress on the ovarian function in adult female mice. Methods In this study, maternal separation in pups was performed during post-natal days 2-14. The histological alterations in ovarian tissue, reactive oxygen species (ROS) production (using 2',7'-dichlorofluorescin diacetate assay), gene expression of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, TLR4, BAX, BCL-2 and TNF-alpha (using RT-PCR), protein levels of ATP, GPx, interleukin (IL)-1 beta and IL-18 (using enzyme-linked immunosorbent assay). Also, protein expression of caspase-3 and NLRP3 (using immunocytochemistry) were evaluated. Results This showed that maternal separation decreased percentage of primordial follicles while increased percentage of secondary and Graafian follicles. In addition, maternal separation increased ROS production and decreased ATP and GPx concentrations. Furthermore, maternal separation significantly affected expression of cytokines and genes involved in inflammation and apoptosis including NLRP3, ASC, caspase-1,TLR4, TNF-alpha, IL-1 beta, IL-18, BAX and BCL2. Findings also showed that stress-induced maternal separation significantly increased percentage of caspase-3 and NLRP3 positive cells. We concluded that maternal separation stress has harmful effects on ovarian tissue. Conclusion It seems that these harmful effects probably occur through increase of ROS production and impact on mitochondrial function, inflammatory process and apoptosis pathways.