Fatty Acid Regulation of the Nrf2/Keap1 Pathway During Mouse Preimplantation Embryo Development
Abstract
Obese women experience frequent infertility; obesity-conditioned reproductive tracts expose embryos to stressors including free fatty acids (FFA). Palmitic acid (PA) exposure significantly impairs mouse preimplantation development and increases endoplasmic reticulum stress; oleic acid (OA) rescues these effects. To further understand FFA in preimplantation development, this thesis investigates the NRF2/KEAP1 pathway, which coordinates antioxidant stress response pathways. We hypothesize that PA induces the NRF2/KEAP1 pathway, while OA alleviates it. Female mice were super-ovulated, mated, and embryos were placed in culture treatments: bovine serum albumin (control), 100 µM PA, 100 µM OA, or 100 µM PA+OA. Protein localization and mRNA abundances were assessed via immunofluorescence and RT-qPCR, respectively. NRF2 displayed nuclear localization throughout preimplantation development. PA significantly decreased NRF2-positive nuclei, while OA and PA+OA did not. FFAs showed no significant effects on relative expression of Nrf2/Keap1. Current results suggest that PA suppresses NRF2/KEAP1 pathway activation, which warrants further investigation as a mechanism for PA-induced developmental impairments.