{"paper_id":"450f4cd1-c49d-4793-b379-7c379dbc179a","body_text":"Abstract\nPurpose: 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).\nMethods: 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.\nResults: 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.\nConclusions: 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.\nSimilar content being viewed by others\nREFERENCES\nWang 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\nSugino 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\nZolti 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\nCicinelli 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\nGriffith OW, Stuehr DJ: Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol 1995;57:707–736\nBrunswig-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\nNagata S: Apoptosis by death factor (review). Cell 1997;88: 355–365\nDimmeler 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\nHsueh AJW, Billing H, Tsafriri A: Ovarian follicle atresia: A hormonally controlled apoptotic process. Endocrinol Rev 1994;15:707–724\nAdashi 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\nRoby, KF, Terranova PF: Tumor necrosis factor alpha alters follicular steroidogenesis in vitro. Endocrinology 1988;123: 2952–2954\nVan Voorhis BJ, Dunn MS, Synder GD, Weiner CP: Nitric oxide: An autocrine regulator of human graulosa-luteal cell steroidogenesis. Endocrinol 1994;135:1799–1806\nRevel 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\nGreen 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\nBen-Rafael Z, Orvieto R: Cytokines-involvement in reproduction. Fertil Steril 1992;58:1093–1099\nZolti 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\nMoncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991;43: 109–142\nRosselli M, Keller PJ, Dubey RK: Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum Reprod Update 1998;4:3–24\nWeiner 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\nZackrisson 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\nJablonkashariff 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\nBeckmann 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\nGeva 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\nCianci 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\nEmoto 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\nKaneto H, Fuji J, Seo HG: Apoptotic cell death triggered by nitric oxide in pancreatic b-cells. Diabetes 1995;44:733–738\nBili 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\nMendoza 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\nAuthor information\nAuthors and Affiliations\nRights and permissions\nAbout this article\nCite this article\nLee, 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\nIssue date:\nDOI: https://doi.org/10.1023/A:1009495913119","source_license":"CC0","license_restricted":false}