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Increased levels of redox-active iron in follicular fluid: A possible cause of free radical - mediated infertility in β-thalassemia major

      Abstract

      OBJECTIVE: Our purpose was to investigate the follicular fluid parameters associated with redox activity and the consequent production of the deleterious hydroxyl radical in β-thalassemia major. STUDY DESIGN: The levels of ferritin, total iron, total copper, and redox-active iron were measured in follicular fluid aspirated from three follicles during three consecutive ovum pickups from a patient with β-thalassemia major and were compared with the levels in nine follicles aspirates from nine healthy control patients. The redox activity in the follicular fluid samples was monitored by the extent of follicular fluid - mediated deoxyribonucleic acid degradation and salicylate hydroxylation. RESULTS: Total iron and ferritin concentrations were elevated in thalassemic follicular fluid samples compared with control samples (6.7-fold and 53.3-fold, respectively), whereas the total copper concentration was similar. Thalassemic follicular fluid samples exhibited a marked increase of redox activity, indicating a higher potential of free radical production leading to deoxyribonucleic acid degradation. Likewise, free radical - induced conversion of salicylate to dihydroxybenzoic acid derivatives was enhanced in the thalassemic follicular fluid samples compared with controls (2,3-dihydroxybenzoic acid: 67.7 ± 22 vs 20.3 ± 12.9 ng/mg protein; 2,5-dihydroxybenzoic acid: 101.6 ± 25.9 vs 4.42 ± 2.7 ng/mg protein). CONCLUSIONS: The increased level of redox activity found in the follicular fluid from a patient with β-thalassemia major focuses the attention on the small fraction of redox-active iron ions as mediators of free radical production, inducing tissue injury and possibly contributing to impairment of reproduction in these patients. (AM J OBSTET GYNECOL 1996;174:914-8.)

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      References

        • Hershko C
        • Pinson A
        • Link G
        Iron chelation.
        Blood Rev. 1990; 4: 1-8
        • Savona-Ventura C
        • Bonello F
        Beta-thalassemia syndromes and pregnancy.
        Obstet Gynecol Surv. 1994; 49: 129-137
        • Borgna-Pignatti C
        • De-Stefano P
        • Zontal L
        • et al.
        Growth and sexual maturation in thalassemia major.
        J Pediatr. 1985; 106: 150-155
        • De-Sanctis V
        • Vullo C
        • Katz M
        • Wonke B
        • Hoffbrand AV
        • Bagni B
        Hypothalamic pituitary gonadal axis in thalassemic patients with secondary amenorrhea.
        Obstet Gynecol. 1988; 72: 643-647
        • Allegra A
        • Carpa M
        • Cuccia L
        • et al.
        Hypogonadism in beta thalassemic adolescents: a characteristic pituitary-gonadal impairment; the ineffectiveness of long-term iron chelating therapy.
        Gynecol Endocrinol. 1990; 4: 181-191
        • Vogt HJ
        • Weidenbach T
        • Marquart KH
        • Vogel GE
        Idiopathic hemochromatosis in a 45 year old infertile man.
        Andrologia. 1987; 19: 532-538
        • Hershko C
        • Graham G
        • Bates GW
        • Rachmilewitz EA
        Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity.
        Br J Haematol. 1978; 40: 25563
        • Halliwell B
        • Gutteridge JMC
        Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts.
        Arch Biochem Biophys. 1986; 246: 501-514
        • Pabon JE
        • Findley WE
        • Gibbon WE
        The toxic effect of short exposures to the atmospheric oxygen concentration on early mouse embryonic development.
        Fertil Steril. 1989; 51: 896-900
        • Legge M
        • Sellens MH
        Free radical scavengers ameliorate the 2-cell block in mouse embryo culture.
        Hum Reprod. 1991; 6: 867-871
        • Reubinoff BE
        • Simon A
        • Friedler S
        • Schenker JG
        • Lewin A
        Defective oocytes as a possible cause of infertility in a beta thalassemia major patient.
        Hum Reprod. 1994; 9: 1143-1145
        • Rund D
        • Cohen T
        • Filon D
        • et al.
        Evolution of a genetic disease in an ethnic isolate: β-thalassemia in the Jews of Kurdistan.
        Proc Natl Acad Sci U S A. 1991; 88: 310-314
        • Konijn AM
        • Levy R
        • Link G
        • Hershko C
        A rapid and sensitive ELIZA for serum ferritin employing a fluorogenic substrate.
        J Immunol Meth. 1982; 54: 297-307
        • Bradford MM
        A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
        Anal Biochem. 1976; 72: 248-253
        • Rothery E
        Varian analytical methods for graphite tube atomizers.
        : Varian, Sugar Land, Texas1988
        • Shreier PH
        • Cortese R
        A fast and simple method for sequencing DNA cloned in the single-stranded bacteriophage M13.
        J Mol Biol. 1979; 129: 169-172
        • Har-El R
        • Chevion M
        Zinc(II) protects against metal-mediated free radical induced damage: studies on single and double-strand DNA breakage.
        Free Radic Res Commun. 1991; 12-13: 509-515
        • Udassin R
        • Ariel I
        • Haskel Y
        • Kitrossky N
        • Chevion M
        Salicylate as an in vivo free radical trap: studies on ischemic insult to the rat intestine.
        Free Radic Biol Med. 1991; 10: 1-6
        • Marklund S
        Spectrophotometric study of spontaneous disproportionation of superoxide anion radical and sensitive direct assay for superoxide dismutase.
        J Biol Chem. 1976; 251: 7504-7507
        • Halliwell B
        The superoxide dismutase activity of iron complexes.
        FEBS Lett. 1975; 56: 34-38
        • Aust SD
        • Morehouse LA
        • Thomas CE
        Role of metals in oxygen radical reactions.
        J Free Radic Biol Med. 1985; 1: 3-25
        • Shiotani M
        • Noda Y
        • Narimoto K
        • et al.
        Immunohistochemical localization of superodismutase in the human ova.
        Hum Reprod. 1991; 6: 1349-1353
        • Chevion M
        • Jiang Y
        • Har-El R
        • Berenshtein E
        • Uretzky G
        • Kitrossky N
        Copper and iron are mobilized following myocardial ischemia: possible predictive criteria for tissue injury.
        Proc Natl Acad Sci U S A. 1993; 90: 1102-1106
        • Chevion M
        A site-specific mechanism for free radical induced biological damage: the essential role of redox active transition metals.
        Free Radic Biol Med. 1988; 5: 27-37
        • Arduini A
        • Eddy L
        • Hochstein P
        The reduction of ferryl myoglobin by ergothioneine: a novel function for ergothioneine.
        Arch Biochem. 1990; 281: 41-43