Downregulative Effects of Nitric Oxide on Oocyte Fertilization and Embryo Development: Possible Roles of Nitric Oxide in the Pathogenesis of Endometriosis-associated Infertility

Abstract

Aims: To investigate the effects of elevated nitric oxide (NO) levels in peritoneal fluids (PF) on oocyte fertilization and pre-implantation embryo development, and the relation of those effects to endometriosis-associated infertility. Methods: PF from women undergoing laparoscopy for infertility of minor endometriosis, tubal blockage and operation for tubal ligation was aspired at the pouch of the cul-de-sac during surgery. Oocytes and embryos of adult ICR mice were cultured in vitro with or without endometriotic PF. The fertilization rate of oocyte and the cleavage rate of 2-cell embryos were examined. Also, the clinical indexes of IVF-ET of women with minor endometriosis and tubal infertility were analyzed. Results: Oocyte fertilization rate of endometriotic women with IVF-ET treatment was significantly lower than that of tubal block women. The dose-related adverse effects of endometriotic PF and SNP (NO donor) in culture medium on oocyte fertilization and embryos development were confirmed. Conclusion: Increased NO levels in PF play an important role in mediating the effects of endometriotic PF on oocyte fertilization and embryo development. IVF might serve as an alternative treatment for endometriosis-associated infertility.

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

“…In a previous study, 10 % or 30 % peritoneal fluid from minimal to mild endometriosis patients decreased the cleavage rate of 2-cell mouse embryos [24]. In the previous report, the effect of 10 % and 30 % peritoneal fluid is similar to the effect of 0.1~10 μM and 1 mM SNP concentration, respectively [24]. Therefore, the concentration of 10 μM SNP used in the present study was able to reflect the microenvironment effect of NO in the patients with endometriosis.…”

“…In previous studies, excess oxidation and high levels of NO within endometrial tissue, follicular fluid, and peritoneal fluid were identified in patients with endometriosis [22,24,41]. Furthermore, studies of single nucleotide polymorphism s reveal that GSTT1 (glutathione-S-transferase) null deletion [36] and eNOS [20] are associated with moderate risk of endometriosis.…”

“…Most reports indicate that the poor oocyte/ embryo quality may be responsible for infertility in patients with endometriosis [11]. Previous studies have reported elevation of nitric oxide (NO) and/or NO synthase (NOS) levels in the endometrial tissue, follicular fluid, and peritoneal fluid of patients with endometriosis [22,24,41]. Furthermore, high levels of serum and follicular NO in patients with endometriosis were associated with poor embryo quality and pregnancy outcome in assisted reproduction technology cycles [22].…”

Role of nitric oxide in motility and fertilizing ability of sperm of Heteropneustes fossilis (Bloch.)

“…The role of NO in regulation of fertilization has also been studied in mammals but results are not consistent with the present findings in catfish. Luo et al (2010) have shown, however, that SNP decreases the fertilization rate in humans. Yang et al (2005) have observed an elevated rate of fertilization in vitro in comparison to the wild type fertilization, when either iNOS-deficient sperm or oocytes were used.…”

Gasotransmitters in Gametogenesis and Early Development: Holy Trinity for Assisted Reproductive Technology—A Review

“…The ambiguous NO necessity could be a result of a more diverse NO effect when NO is associated with inflammation and/or oxidative stress [47, 48]. Accordingly, the role of NO during subsequent embryonic development after fertilization remains controversial [49–51] for inflammation (endometriosis), accompanying NO [52, 53] and protein nitration [54]. However, creation of secondary products of NO interactions seems to be one of possible mechanisms of NO negative action [55].…”