Beta-aminoisobutyric acid improves bovine oocyte maturation and subsequent embryonic development by promoting lipid catabolism

Abstract

Energy metabolism homeostasis is essential for oocyte maturation and acquisition of developmental capacity. However, bovine oocyte in vitro maturation (IVM) is highly susceptible to metabolic stress and lipid accumulation. β-Aminoisobutyric acid (BAIBA), a metabolite produced in response to skeletal muscle exercise, has been reported to be involved in lipid and glucose metabolism, as well as inflammation and oxidative stress. This work aimed to evaluate the potential effects of BAIBA on bovine oocyte IVM and its mechanisms. Different concentrations of BAIBA (10, 20, 50, 100, and 200 μmol/L) were supplemented to bovine oocyte IVM medium. Results shown the BAIBA (50 μmol/L) had no effect on the extrusion rate of the first polar body of oocytes but significantly improved the subsequent blastocyst formation rate and embryo quality. Further revealed that supplementing BAIBA significantly up-regulated expression levels of genes to fatty acid β-oxidation metabolism (CPT1A, CPT1B and CPT2), promoted lipid metabolism, lowered lipid content, and improved mitochondrial membrane potential and active mitochondria content. Importantly, BAIBA stimulation significantly increased the phosphorylation of AMP-activated protein kinase (AMPK); and the inhibition of AMPK activity (Compound C, AMPK inhibitor) suppressed the ability of BAIBA to promote lipid metabolism in oocytes. Besides, inhibition of AMPK lowered the oocyte maturation rate and the subsequent zygote cleavage and blastocyst formation rate when compared to that of the BAIBA treatment. The results indicated that BAIBA was mainly involved in promoting lipid catabolism by activation of AMPK, consequently enhancing oocyte development potential.