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Relationships Between Concentrations of Tumor Necrosis Factor-α and Nitric Oxide in Follicular Fluid and Oocyte Quality

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Abstract

Purpose: Our objective was to explain a relationshipbetween concentrations of tumor necrosis factor-α (TNF-α)and nitric oxide (NO) in follicular fluid, oocyte quality, andoutcomes of in vitro fertilization=nembryo transfer (IVF-ET).

Methods: The concentrations of TNF-α and NO weremeasured in 115 follicular fluid samples collected from 43patients undergoing IVF-ET program, due to tubalobstruction, some with endometriosis (8 patients) or hydrosalpinx(5 patients). A correlation of these factors concentrationsand the oocyte quality, the oocyte maturity, andinfertility-associated diseases was analyzed.

Results: No correlation was found between concentrationsof NO and TNF-α in follicular fluid. NO concentrations infollicular fluids were significantly higher in patients withendometriosis (P < 0.001) or hydrosalpinx (P < 0.01)compared to the patients with just tubal obstruction. FollicularNO concentration differences according to oocyte maturityand oocyte quality were not found. In contrast, TNF-αconcentrations in follicular fluids were significantly higher inpoor quality oocytes (P < 0.05) but were not associatedwith infertility-associated diseases, such as hydrosalphinxor endometriosis, and the oocyte maturity. No significantdifferences in follicular levels of NO and TNF-α as well asIVF-ET parameters of pregnant and nonpregnant groupswere revealed.

Conclusions: There is no significant correlation betweenthe concentrations of NO and TNF-α in follicular fluid. NOlevels in follicular fluid are altered in infertility-associateddiseases. However, TNF-α levels but not NO levels influenceoocyte quality. These results suggest that the production ofNO and TNF-α in follicular fluid may be regulated viadifferent pathways and can be tempered withinfertility-associated diseases, thereby influencing oocyte qualitylocally.

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REFERENCES

  1. Wang LJ, Brannstorm M, Robertson SA, Norman RJ: Tumor necrosis factor a in human ovary: Presence in follicular fluid and effects on cell proliferation and prostaglandin production. Fertil Steril 1992;58:934–940

    Google Scholar 

  2. Sugino N, Takiguchi S, Ono M, Tamura H, Shimamura K, Nakamura Y, Tsuruta R, Sadamitsu D, Ueda T, Maekawa T, Kato H: Nitric oxide concentrations in the follicular fluid and apoptosis of granulosa cells in human follicles. Hum Reprod 1996;11:2484–2487

    Google Scholar 

  3. Zolti M, Bider D, Seidman DS, Mashiach S, Ben-Rafael Z: Cytokines levels in follicular fluid of polycystic ovaries in patients treated with dexamethasone. Fertil Steril 1992;57: 501–504

    Google Scholar 

  4. Cicinelli E, Ignarro L, Lograno M, Galantino P, Balzano G, Schonauer LM: Circulating levels of nitric oxide in fertile women in relation to the menstrual cycle. Fertil Steril 1996; 66:1036–1038

    Google Scholar 

  5. Griffith OW, Stuehr DJ: Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol 1995;57:707–736

    Google Scholar 

  6. Brunswig-Spickenheire B, Mukhopadhyay AK: Stimulation of nitric oxide cyclic guanosine monophosphate pathway in bovine ovarian theca cells by tumor necrosis factor a (TNF-a). Is this pathway implicated in the TNF-a induced inhibition of luteinizing hormone-stimulated prorenin production? Biol Reprod 1997;57:700–706

    Google Scholar 

  7. Nagata S: Apoptosis by death factor (review). Cell 1997;88: 355–365

    Google Scholar 

  8. Dimmeler S, and Zeiher AM: Nitric oxide and apoptosis: Another paradigm for her double-edged role of nitric oxide. Nitric Oxide: Biol Chem 1997;1:275–281

    Google Scholar 

  9. Hsueh AJW, Billing H, Tsafriri A: Ovarian follicle atresia: A hormonally controlled apoptotic process. Endocrinol Rev 1994;15:707–724

    Google Scholar 

  10. Adashi EY, Resnick CE, Packman JN, Hurwitz A, Payne DW: Cytokine-mediated regulation of ovarian function: Tumor necrosis factor a inhibits gonadotropin-supported progesterone accumulation by differentiating and luteinized murine granulosa cells. Am J Obstet Gynecol 1990;162:889–894

    Google Scholar 

  11. Roby, KF, Terranova PF: Tumor necrosis factor alpha alters follicular steroidogenesis in vitro. Endocrinology 1988;123: 2952–2954

    Google Scholar 

  12. Van Voorhis BJ, Dunn MS, Synder GD, Weiner CP: Nitric oxide: An autocrine regulator of human graulosa-luteal cell steroidogenesis. Endocrinol 1994;135:1799–1806

    Google Scholar 

  13. Revel A, Barak V, Lavy Y, Anteby E, Abramov Y, Schenker JJ, Amit A, Mayer M, Simon A, Laufer N, Hurwitz A: Characterization of intraperitoneal cytokines and nitrites in women with severe ovarian hyperstimulation syndrome. Fertil Steril 1996;66:66–71

    Google Scholar 

  14. Green LC, Wager DA, Glogowsky J, Skipper PL. Wishnok JS, Tannenbaum SR: Analysis of nitrate, nitrite and 15N nitrate in biological fluids. Anal Biochem 1982;126:131–138

    Google Scholar 

  15. Ben-Rafael Z, Orvieto R: Cytokines-involvement in reproduction. Fertil Steril 1992;58:1093–1099

    Google Scholar 

  16. Zolti M, Meirom R, Shemesh M, Wallach D, Mashiach S, Shore L: Granulosa cells as source and target organ for tumor necrosis factor-α. FEBS Lett 1990;261:253–255

    Google Scholar 

  17. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43: 109–142

    Google Scholar 

  18. Rosselli M, Keller PJ, Dubey RK: Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 1998;4:3–24

    Google Scholar 

  19. Weiner CP, Lisasoain I, Baylis S, Knowles R, Charles I, Monacada S: Induction of calcium-dependent nitric oxide synthases by sex hormones. Proc Natl Acad Sci USA 1994;19:5212–5216

    Google Scholar 

  20. Zackrisson U, Mikuni M, William A: Cell specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. Hum Reprod 1996;11:2667–2673

    Google Scholar 

  21. Jablonkashariff A, Olson LM: Hormonal regulation of nitric oxide synthase and their cell-specific expression during follicular development in the rat ovary. Endocrinol 1997;130:460–468

    Google Scholar 

  22. Beckmann MW, Polacek D, Sewun L, Schreiber JR: Human ovarian granulosa cell culture: Determination of blood cell contamination and evaluation of possible purification steps. Fertil Steril 1991;56:881–887

    Google Scholar 

  23. Geva E, Lessing JB, Lerner-Geva L, Azem F, Yovel L, Amit A: Elevated levels of interleukin-6 in the follicular fluid at the time of oocyte retrieval for in vitro fertilization may predict the development of early-form ovarian hyperstimulation syndrome. Fertil Steril 1997;68:133–137

    Google Scholar 

  24. Cianci A, Calogero AE, Palumbo MA, Burrello N, Ciotta L, Palumbo G, Bernardini R: Relationship between tumor necrosis factor-a and sex steroid concentrations in the follicular fluid of women with immunological infertility. Hum Reprod 1996; 11:265–268

    Google Scholar 

  25. Emoto S, Baird A: The effect of tumor necrosis factor/cachectin on follicle-stimulating hormone-induced aromatase activity in rat granulosa cells. Biochem Biophys Res Commun 1988;153: 792–798

    Google Scholar 

  26. Kaneto H, Fuji J, Seo HG: Apoptotic cell death triggered by nitric oxide in pancreatic b-cells. Diabetes 1995;44:733–738

    Google Scholar 

  27. Bili H, Tarlatzis BC, Danilidis M, Fleva A, Bontis J, Tourkanterizationtonis A, Mantalenakis S: Cytokines in human ovary: Presence in follicular fluid and correlation with leukotriene B4. J Assist Reprod Genet 1998;15:93–98

    Google Scholar 

  28. Mendoza C, Cremades N, Ruiz-Requena E, Martinerz F, Ortega E, Bernabeu S, Tesarik J: Relationship between fertilization results after intracytoplasmic sperm injection, and intrafollicular steroid, pituitary hormone and cytokine concentations. Hum Reprod 1999;14:628–635

    Google Scholar 

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Pusan, Korea

    Kyu Sup Lee, Yong Jin Na, Man Soo Yoon, Ook Hwan Choi & Won Whe Kim

  2. Department of Obstetrics and Gynecology, Pusan National University School of Medicine, 1–10 Amidong, Seoku, Pusan, 602–739, Korea

    Kyu Sup Lee

  3. Center for Reproductive Medicine and Infertility, Moonhwa Hospital, Pusan, Korea

    Bo Sun Joo

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  1. Kyu Sup Lee
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  2. Bo Sun Joo
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Lee, K.S., Joo, B.S., Na, Y.J. et al. Relationships Between Concentrations of Tumor Necrosis Factor-α and Nitric Oxide in Follicular Fluid and Oocyte Quality. J Assist Reprod Genet 17, 222–228 (2000). https://doi.org/10.1023/A:1009495913119

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  • DOI: https://doi.org/10.1023/A:1009495913119

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