NO is necessary and sufficient for egg activation at fertilization

Kuo, Richard C.; Baxter, Gregory T.; Thompson, Stuart H.; Stricker, Stephen A.; Patton, Chris; Bonaventura, Joseph; Epel, David

doi:10.1038/35020577

Cited by 155 publications

(117 citation statements)

References 24 publications

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“…NO is a highly diffusible molecule that plays an important role in mammalian reproductive function, including folliculogenesis [14], fertilization [21], and implantation [7]. Endogenous NO is produced following the conversion of oxygen and L-arginine to NO and L-citrulline, catalyzed by three isoforms of NOS: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) [12].…”

Section: Introductionmentioning

confidence: 99%

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

Lee¹,

Lee²,

Huang³

et al. 2013

J Assist Reprod Genet

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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.

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Section: Introductionmentioning

confidence: 99%

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

Lee¹,

Lee²,

Huang³

et al. 2013

J Assist Reprod Genet

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“…However, the physiological significance of RyR-mediated [Ca 2+ ] i oscilla-tions is questionable, since they do not lead to full egg activation (Ayabe et al, 1995;Fissore et al, 1995;Wu et al, 1997), and because inhibition of this receptor does not perturb fertilization-induced egg activation (Ayabe et al, 1995). The suggestion was also made, based on results from studies in sea urchin eggs, that synthesis of nitric oxide (NO) may act as the initiator of [Ca 2+ ] i release (Kuo et al, 2000). However, studies in ascidian and mouse eggs revealed that fertilizationassociated [Ca 2+ ] i oscillations occur independently of changes in NO concentrations (Hyslop et al, 2001).…”

Section: Fertilization and Inositol 145-trisphosphate (Ip 3 ) Produmentioning

confidence: 99%

Mammalian Fertilization: From Sperm Factor to Phospholipase Cζ

Kurokawa

Sato

Fissore

2004

Biology of the Cell

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In mammalian eggs, the fertilizing sperm evokes intracellular Ca 2+ ([Ca 2+ ] i ) oscillations that are essential for initiation of egg activation and embryonic development. Although the exact mechanism leading to initiation of [Ca 2+ ] i oscillations still remains unclear, accumulating studies suggest that a presently unknown substance, termed sperm factor (SF), is delivered from the fertilizing sperm into the ooplasm and triggers [Ca 2+ ] i oscillations. Based on findings showing that production of inositol 1,4,5-trisphosphate (IP 3 ) underlies the generation of [Ca 2+ ] i oscillations, it has been suggested that SF functions either as a phospholipase C (PLC), an enzyme that catalyzes the generation of IP 3 , or as an activator of a PLC(s) pre-existing in the egg. This review discusses the role of SF as the molecule responsible for the production of IP 3 and the initiator of [Ca 2+ ] i oscillations in mammalian fertilization, with particular emphasis on the possible involvement of egg-and sperm-derived PLCs, including PLCf, a novel sperm specific PLC.

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“…3 For instance, nNOS plays a fundamental role in the regulation of male sexual function. Lines of evidence have indicated the involvement of nNOS in penile erection, 4 in testosterone synthesis in the Leydig cells of the testis, 5,6 in sexual behavior, [7][8][9] and in egg activation at fertilization, 10 among others. Understanding the molecular regulation of nNOS in male sexual organs may be relevant to potential therapeutic measures in male sexual dysfunction.…”

mentioning

confidence: 99%

An Alternative Promoter of the Human Neuronal Nitric Oxide Synthase Gene Is Expressed Specifically in Leydig Cells

Wang¹,

Newton²,

Miller³

et al. 2002

The American Journal of Pathology

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Neuronal nitric oxide synthase (nNOS) plays a modulatory role in the biology of a variety of neuroendocrine tissues and is especially relevant to gonadal function. We have previously reported the cloning and characterization of a variant of the nNOS protein, termed testis nNOS (TnNOS), the mRNA for which was restricted in expression to male gonadal tissues. To examine the cell-specificity of the testis-specific NOS regulatory regions we defined patterns of ␤-galactosidase expression of an insertional transgene in which the reporter gene lacZ was under the transcriptional control of the human TnNOS promoter. ␤-galactosidase activity was detected exclusively in the interstitial cells of the testis in transgenic mice. These cells also evidenced positive staining for nNOS protein and were identified as androgen-producing Leydig cells by staining with the Leydig cell marker, P 450 scc. Expression of the promoter was absent in cells of the seminiferous tubules, specifically germline cells of different stages and Sertoli cells. In contrast to the male gonad, ␤-galactosidase activity was not detected in ovaries of adult female mice. Activity was also not evident in organs known to express full-length nNOS, such as skeletal muscle, kidney, or cerebellum. The same pattern of ␤-galactosidase staining was observed in independent transgenic founders and was distinct from that observed for an endothelial NOS promoter/reporter transgene. In the testis of male adult eNOS promoter-reporter transgenic mice, ␤-galactosidase activity was expressed only in endothelial cells of large-and medium-sized arterial blood vessels. Transcriptional activity of the Of the three known human nitric oxide synthases (NOS) isoforms, the neuronal nitric oxide synthase (nNOS) has unique properties. The nNOS (NOS1) isoform is expressed from a very complex human genomic locus spanning 240 kb at 12q24.2.

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NO is necessary and sufficient for egg activation at fertilization

Cited by 155 publications

References 24 publications

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

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

Mammalian Fertilization: From Sperm Factor to Phospholipase Cζ

An Alternative Promoter of the Human Neuronal Nitric Oxide Synthase Gene Is Expressed Specifically in Leydig Cells

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