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

Tsung Hsien Lee, Maw Sheng Lee, Chun Chia Huang, Hui Mei Tsao, Pi Mei Lin, Hong Nerng Ho, Jin Yuh Shew, Yu Shih Yang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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. Methods: Zygotes from superovulated B6CBF1 mice were cultured to blastocysts in a variety of media. Sodium nitroprusside (SNP) and N G-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.

Original languageEnglish
Pages (from-to)1063-1072
Number of pages10
JournalJournal of Assisted Reproduction and Genetics
Volume30
Issue number8
DOIs
Publication statusPublished - Aug 1 2013
Externally publishedYes

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Protein S
Embryonic Development
Nitric Oxide
Apoptosis
Blastocyst
Superoxides
Endoplasmic Reticulum
Glutathione
Culture Media
Mitochondria
Embryonic Structures
Adenosine Triphosphate
Nitric Oxide Donors
Zygote
Cyclic GMP
Nitroprusside
Endometriosis
Confocal Microscopy
Nitric Oxide Synthase
Arginine

Keywords

  • Apoptosis
  • Embryo development
  • Mitochondria
  • Nitric oxide
  • S-nitrosylation

ASJC Scopus subject areas

  • Reproductive Medicine
  • Genetics
  • Obstetrics and Gynaecology
  • Developmental Biology
  • Genetics(clinical)

Cite this

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development. / Lee, Tsung Hsien; Lee, Maw Sheng; Huang, Chun Chia; Tsao, Hui Mei; Lin, Pi Mei; Ho, Hong Nerng; Shew, Jin Yuh; Yang, Yu Shih.

In: Journal of Assisted Reproduction and Genetics, Vol. 30, No. 8, 01.08.2013, p. 1063-1072.

Research output: Contribution to journalArticle

Lee, Tsung Hsien ; Lee, Maw Sheng ; Huang, Chun Chia ; Tsao, Hui Mei ; Lin, Pi Mei ; Ho, Hong Nerng ; Shew, Jin Yuh ; Yang, Yu Shih. / Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development. In: Journal of Assisted Reproduction and Genetics. 2013 ; Vol. 30, No. 8. pp. 1063-1072.
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AU - Lee, Tsung Hsien

AU - Lee, Maw Sheng

AU - Huang, Chun Chia

AU - Tsao, Hui Mei

AU - Lin, Pi Mei

AU - Ho, Hong Nerng

AU - Shew, Jin Yuh

AU - Yang, Yu Shih

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N2 - 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. Methods: Zygotes from superovulated B6CBF1 mice were cultured to blastocysts in a variety of media. Sodium nitroprusside (SNP) and N G-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.

AB - 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. Methods: Zygotes from superovulated B6CBF1 mice were cultured to blastocysts in a variety of media. Sodium nitroprusside (SNP) and N G-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.

KW - Apoptosis

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KW - Nitric oxide

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