The attenuation of the toxic effects of LPS on mouse pre-implantation development by alpha-lipoic acid

Abstract

The present study was conducted to evaluate the effects of alpha-lipoic acid (ALA) on quantitative and qualitative indices of mouse embryos challenged by lipopolysaccharide (LPS). Having determined the effective concentrations of LPS (1 mg/mL) that could reduce blastocyst formation rate by around 50% and the optimal concentration of ALA (10 μM) that could attenuate the toxic effects of LPS on blastocyst formation, the following indices were defined: inner cell mass and trophectoderm cell numbers, blastocyst mitochondrial distribution, ROS and GSH levels, as well as the relative expression of Tlr-4. Nrf-2 and Tnf-RI/P-60 receptor involved in inflammatory pathways. Finally, embryos derived from the experimental and control groups were transferred to synchronized recipients and their implantation rate and post-implantation capacity were determined. Treatment with LPS resulted in an increase in intracellular ROS level (P ≤ 0.05), and remarkable decreases (P ≤ 0.05) in intracellular GSH content, mitochondrial mass, and blastocyst quality. ALA attenuated all the aforementioned negative effects of LPS. The relative expression levels of Nrf-2 and Tnf-RI/P-60 receptor (P ≤ 0.05) significantly increased in response to LPS, and treatment with ALA significantly reduced the relative expression of Tnf-RI/P-60. ALA also improved the post-implantation developmental capacity of embryos treated with LPS. In conclusion, our findings indicate that the reproductive toxicity of LPS could be overcome by ALA treatment. These effects were mainly due to the improvements made in intracellular antioxidant capacity as well as suppression of some inflammatory elements, especially the main receptor of TNF-α, the Tnf-RI/P-60, involved in induction of apoptosis. These observations have important implications for dairy farming and treatment of infertility.