Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

Purpose Previous studies reported that patients with endometriosis had excess nitric oxide (NO) in the reproductive tract and poor embryo development in IVF cycles. This study aims to elucidate the effects of NO on early embryo development.

Zygotes from superovulated B6CBF1 mice were cultured to blastocysts in a variety of media. Sodium nitroprusside (SNP) and NG-nitro-L-arginine (LNA) were added to the culture medium as a NO donor and a NO synthase inhibitor, respectively. The localization and fluorescence intensity of S-nitrosylated (SNO) proteins within 2-cell stage embryos were analyzed with confocal microscopy. Apoptosis and ATP production in the blastocysts were measured. Result(s) Subsequent to NO exposure, the SNO proteins mainly colocalized with the mitochondria and endoplasmic reticulum and the intensity of SNO proteins increased. The addition of a quanylate cyclase inhibitor and a cyclic GMP mimic agent induced nonsignificant changes in SNO proteins, whereas addition of a superoxide scavenger or a reduced form of glutathione rescued the embryos from the effects of NO. However, superoxide scavenger supplementation resulted in decreased blastocyst ATP production. Conclusion(s) Elevated NO exerts deleterious effects on embryo development, possibly through protein S-nitrosylation in the mitochondria and endoplasmic reticulum. Including glutathione as a component in the culture medium might counteract this effect. Similar content being viewed by others

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JY Shew and YS Yang approved the final version of manuscript. Conflict of interest All the authors have no conflicts of interest to declare. Author information Authors and Affiliations Corresponding author Additional information Capsule Excessive environmental nitric oxide is detrimental to embryo development through protein S-nitrosylation in the mitochondria and endoplasmic reticulum. Glutathione supplementation could counteract such effect. Rights and permissions About this article Cite this article Lee, TH., Lee, MS., Huang, CC. et al. Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development. J Assist Reprod Genet 30, 1063–1072 (2013). https://doi.org/10.1007/s10815-013-0045-7 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s10815-013-0045-7