Obese women experience greater incidence of infertility, with reproductive tracts exposing preimplantation embryos to elevated free fatty acids (FFA) such as palmitic acid (PA) and oleic acid (OA). PA treatment impairs mouse preimplantation development in vitro, while OA co-treatment rescues blastocyst development of PA treated embryos. In the present study, we investigated the effects of PA and OA treatment on NRF2/Keap1 localization, and relative antioxidant enzyme (Glutathione peroxidase; Gpx1, Catalase; Cat, Superoxide dismutase; Sod1 and γ-Glutamylcysteine ligase catalytic unit; Gclc) mRNA levels, during in vitro mouse preimplantation embryo development. Female mice were superovulated, mated, and embryos cultured in the presence of bovine Serum albumin (BSA) control or PA, or OA, alone (each at 100 μM) or PA + OA combined (each at 100 μM) treatment. NRF2 displayed nuclear localization at all developmental stages, whereas Keap1 primarily displayed cytoplasmic localization throughout control mouse preimplantation development in vitro. Relative transcript levels of Nrf2, Keap1, and downstream antioxidants significantly increased throughout control mouse preimplantation development in vitro. PA treatment significantly decreased blastocyst development and the levels of nuclear NRF2, while OA and PA + OA treatments did not. PA and OA treatments did not impact relative mRNA levels of Nrf2, Keap1, Gpx1, Cat, Sod1 or Gclc. Our outcomes demonstrate that cultured mouse embryos display nuclear NRF2, but that PA treatment reduces nuclear NRF2 and thus likely impacts NRF2/KEAP1 stress response mechanisms. Further studies should investigate whether free fatty acid effects on NRF2/KEAP1 contribute to the reduced fertility displayed by obese patients.

肥胖女性的不孕症发生率更高，因为生殖道使植入前胚胎暴露于升高的游离脂肪酸 (FFA)，例如棕榈酸 (PA) 和油酸 (OA)。PA 处理会损害小鼠体外植入前发育，而 OA 联合治疗可挽救 PA 处理胚胎的囊胚发育。在本研究中，我们研究了 PA 和 OA 处理对 NRF2/Keap1 定位和相关抗氧化酶（谷胱甘肽过氧化物酶；Gpx1，过氧化氢酶；Cat，超氧化物歧化酶；Sod1和 γ-谷氨酰半胱氨酸连接酶催化单元；Gclc）mRNA 水平的影响,在体外小鼠植入前胚胎发育。雌性小鼠在牛血清白蛋白 (BSA) 对照或 PA 或 OA 单独（各 100 μM）或 PA + OA 组合（各 100 μM）处理存在的情况下进行超排卵、交配和培养胚胎。NRF2 在所有发育阶段都显示核定位，而 Keap1 在整个对照小鼠植入前体外发育过程中主要显示细胞质定位。Nrf2、Keap1和下游抗氧化剂的相对转录水平在整个对照小鼠植入前体外发育过程中显着增加. PA 处理显着降低囊胚发育和核 NRF2 水平，而 OA 和 PA + OA 处理则没有。PA 和 OA 处理不影响Nrf2、Keap1、Gpx1、Cat、Sod1或Gclc的相对 mRNA 水平。我们的结果表明，培养的小鼠胚胎显示核 NRF2，但 PA 处理减少了核 NRF2，因此可能影响 NRF2/KEAP1 应激反应机制。进一步的研究应该调查游离脂肪酸对 NRF2/KEAP1 的影响是否会导致肥胖患者的生育能力下降。