Impaired mitochondrial function in the preimplantation embryo perturbs fetal and placental development in the mouse.

The preimplantation embryo is sensitive to its environment and, despite having some plasticity to adapt, environmental perturbations can impair embryo development, metabolic homeostasis, fetal and placental development, and offspring health. This study used an in vitro model of embryo culture with increasing mitochondrial inhibition to directly establish the effect of impaired mitochondrial function on embryonic, fetal, and placental development. Culture in the absence of the carbohydrate pyruvate significantly increased blastocyst glucose oxidation via glycolysis to maintain normal levels of ATP and tricarboxylic acid (TCA) cycle activity. This culture resulted in a significant reduction in blastocyst development, trophectoderm cell number, and respiration rate but, importantly, did not impair implantation rates or fetal and placental development. In contrast, increasing concentrations of the mitochondrial inhibitor amino-oxyacetate (AOA) impaired glycolysis, TCA cycle activity, respiration rate, and ATP production; incrementally reduced blastocyst development; and decreased blastocyst inner cell mass and trophectoderm cell numbers. Importantly, AOA did not affect implantation rates; however, 5 µM AOA significantly reduced placental growth but not fetal growth, increasing the fetal:placental weight ratio. Furthermore, 50 µM AOA significantly reduced both placental and fetal growth but not the fetal:placental weight ratio. Hence, this study demonstrates that a threshold of mitochondrial function is required for normal development, and despite developmental plasticity of the embryo, impaired mitochondrial function in the embryo affects subsequent fetal and placental growth. These results highlight the importance of mitochondrial function in regulating pre- and postimplantation development; however, the effect on offspring health remains unknown.

Maternal supply of omega-3 polyunsaturated fatty acids alter mechanisms involved in oocyte and early embryo development in the mouse.

Despite the well-known benefits of omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on human health, relatively little is known about the effect of n-3 PUFA intake on fertility. More specifically, the aim of this study was to determine how oocyte and preimplantation embryo development might be influenced by n-3 PUFA supply and to understand the possible mechanisms underlying these effects. Adult female mice were fed a control diet or a diet relatively high in the long-chain n-3 PUFAs for 4 wk, and ovulated oocytes or zygotes were collected after gonadotropin stimulation. Oocytes were examined for mitochondrial parameters (active mitochondrial distribution, mitochondrial calcium and membrane potential) and oxidative stress, and embryo developmental ability was assessed at the blastocyst stage following 1) in vitro fertilization (IVF) or 2) culture of in vivo-derived zygotes. This study demonstrated that exposure of the oocyte during maturation in the ovary to an environment high in n-3 PUFA resulted in altered mitochondrial distribution and calcium levels and increased production of reactive oxygen species. Despite normal fertilization and development in vitro following IVF, the exposure of oocytes to an environment high in n-3 PUFA during in vivo fertilization adversely affected the morphological appearance of the embryo and decreased developmental ability to the blastocyst stage. This study suggests that high maternal dietary n-3 PUFA exposure periconception reduces normal embryo development in the mouse and is associated with perturbed mitochondrial metabolism, raising questions regarding supplementation with n-3 PUFAs during this period of time.