Nitric Oxide Synthase Production and Nitric Oxide Regulation of Preimplantation Embryo Development

2003/05/01 by Susanne Tranguch, Nury Steuerwald, Yvette M. Huet-Hudson +1 · 102 citations
Medicine · Psychology · #Andrology #Biology #Blastocyst #Cardiovascular Issues in Pregnancy #Cell biology #Embryo #Embryogenesis #Endocrinology #Endothelial NOS #Enos #Neuroendocrine regulation and behavior #Nitric Oxide and Endothelin Effects #Nitric oxide #Nitric oxide synthase

paper · pdf · doi:10.1095/biolreprod.102.009282

published in Biology of Reproduction 68(5), 1538-1544 (Oxford University Press)

openalex publication_date 2003/05/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

Abstract

Nitric oxide (NO) production plays an important role in regulating preimplantation embryo development. NO is produced from l-arginine by the enzyme nitric oxide synthase (NOS), which has three isoforms: endothelial (eNOS), neuronal (nNOS), and inducible (iNOS). It has been previously shown that inhibition of NO production by NG-nitro-l-arginine (l-NA) inhibits the development of two-cell embryos to the four-cell stage. However, excess NO also halts embryo development, possibly through the production of free radicals. We hypothesize that multiple NOS isoforms are expressed in order to ensure normal preimplantation embryo development and that, in this process, NO acts through the cGMP pathway. Using reverse transcription-polymerase chain reaction, mRNA for all three NOS isoforms was amplified from two-cell, four-cell, morula, and blastocyst embryos. However, blastocyst-stage embryos isolated midmorning on Day 4 of pregnancy expressed only nNOS and eNOS, whereas those isolated midafternoon again expressed all three NOS isoforms. Culture of one-cell embryos in various concentrations of Whitten (positive control), S-nitroso-N-acetylpenicillamine (SNP, a NO donor), l-NA, and/or 8-Br-cGMP demonstrated that NO is acting, at least in part, through cGMP in preimplantation embryo development. In addition, we determined that a critical concentration of NO and cGMP is required for normal embryo development and deviations from this concentration lead to developmental arrest and/or apoptosis of the embryo. This data provides support for a requirement of NO in preimplantation embryo development and one mechanism through which it regulates mitotic division in these embryos.

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