Chronic a administration of nonsteroidal - antiinflammatory drugs (NDAIDS): effects upon mouse reproductive funcions
Keywords:
nonsteroidal-antiinflamatory drugs, prostaglandins, reproduction, sperm functional activity, oocyte, ibuprofen, piroxicamAbstract
Although nonsteroidal-antiinflamatory drugs (NSAIDs) are widely employed, reproductive side effects of prostaglandins long-term inhibition remain unknown. The objective of the present study wasto evaluate the effects of chronic low/moderate NSAIDs doses upon mice reproductive functions. Male or female mice were injected (i.p. for 60 or 35 days respectively) with: ibuprofen doses A, B or C (0.56, 1.12 or 1.68mg/100g/day respectively) or piroxicam doses A, B or C (0.028, 0.056 or 0.084mg/100g/day respectively). Parameters evaluated were: a) in females, spontaneous and induced ovulation, oocyte maturity and spermatozoa migration through genital tract, b) in males, epididymal spermatozoa concentration, motility, viability, resistance to hypoosmotic shock, acrosomal status and membrane maturity and c) in both genders, in vitro and in vivo fertilization, reproductive hormones plasma levels and cyclooxigenase inhibition in reproductive tissues. In females ibuprofen (dose A) elicited a significant reduction in spontaneous and induced ovulation rates and piroxicam (dose A) diminished the concentration of spermatozoa found in the uterus after mating. Males treated with ibuprofen (dose B) showed a reduction in the in vitro fertilization ability. Our data reveal that chronic administration of ibuprofen or piroxicam can exert detrimental effects upon reproductive physiology, which depends on the doses and/or the drug employed.
Downloads
Download data is not yet available.
References
Aitken RJ, Kelly RW: Analysis of the direct effects of prostaglandins on human sperm function. J Reprod Fertil; 1985, 73: 139-146.
Bygdeman M, Gottlieb C, Svanborg K, Swahn ML: Role of prostagalndins in human reproduction: recent advances. Adv Thromb Leukot Res; 1987, 17: 1112-1116.
Casalino SM, Linares JA, Goldraij A: Influence of underfeeding on the spontaneous contraction and on metabolism of labelled arachidonic acid in uteri isolated from intact and ovariectomized rats. Prostaglandins Leukot Essent Fatty Acids; 1996, 55: 155-158.
Clavert A, Cranz C, Bollack C: Functions of the seminal vesicle. Andrologia; 1990, 22: 185-192.
Dawood My: Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol; 1993, 169: 1255-1265.
Duffy DM, Stouffer RL: The ovulatory gonadotrophin surge stimulates cyclooxygenase expression and prostaglandin production by the monkey follicle. Mol Hum Reprod; 2001, 7: 731-739.
Espey LL, Kohda H, Mori T, Okamura H: Rat ovarian prostaglandin levels and ovulation as indicators of the strengh of non-steroidal anti-inflammatory drugs. Prostaglandins; 1988, 36: 875-879.
Espey LL, Stein VI, Dumitrescu J: Survey of antiinflammatory agents and related drugs as inhibitors of ovulation in the rabbit. Fertil Steril; 1982, 38: 238-247.
Farr CH, Ellis LW: In vitro contractility of ratseminiferous tubules in response to prostaglandin, cyclic GMP, testosterone and 2,4-dibromoacetophenone. J Reprod Fertil; 1980, 58: 37-42.
Fiol De Cuneo, M, Ruiz RD, Ponce AA, Maldonado X, Lacuara JL: Time-related 11- changes in functional activity of mouse spermatozoa during in vitro or in vivo incubation. J Exp Anim Sci; 1994, 36: 189-200.
Fraser LR: Calciun channels play a pivotal role in the sequence of ionic change involved in initiation of mouse sperm acrosomal exocytosis. Mol Reprod Dev; 1993, 36: 368- 376.
Gurevich M, Harel-Markowitz E, Marcus S, Shore LS, Shemesh M: Prostaglandin production by the oocyte cumulus complex around the time of fertilization and the effect of prostaglandin E on the development of the early embryo. Reprod Fertil Dev; 1993, 5: 281-283.
Hayashi S, Noda Y, Mori T: Analysis of the role of prostaglandins in the fertilization process. Eur J Obstet Gynecol Reprod Biol; 1988, 29: 287-297.
Herrero MB, Franchi AM, Gimeno MAF: Mouse spermatozoa can synthesize PGE2 and 5-HETE in vitro: stimulatory action of nitric oxide. Prostaglandins Leukot Essent Fatty Acids; 1995, 53: 347-350.
Joyce CL, Nuzzo NA, Wilson L, Zaneveld LJD: Evidence for a role of cyclooxigenase (prostaglandin synthetase) and prostaglandins in sperm acrosome reaction and fertilization. J Androl; 1987, 8: 74-82.
Katz E, Dharmarajan AM, Sueoka K, Ghodganonkar RB, Dubin NH, Wallach EE: Effects of systemic administration of indomethacin on ovulation, luteinization, and steroidogenesis in the rabbit ovary. Am J Obstet Gynecol; 1989, 161: 1361-1366.
Knuth UA, Kühne J, Crosby J, Bals-Pratsch M, Kelly RW, Nieschlag E: Indomethacin and oxaprozin lower seminal prostaglandin levels but do not influence sperm motion characteristics and serum hormones of young healthy men in placebo-controlled double-blind trial. J Androl; 1989, 10: 108-119.
Löscher W, Lüttgenau H, Schlegel W, Krüger S: Pharmacokinetics of non-steroidal anti-inflammatory drugs in male rabbits after acute and chronic administration and effect of chronic treatment on seminal prostaglandins, sperm quality and fertility. J Reprod Fert; 1988, 82: 353-364.
Makler A: The improved ten-micrometer chamber for rapid sperm count and motility evaluation. Fertil Steril; 1980, 33: 337-338.
Martini AC, Fiol De Cuneo M, Ruiz RD, Ponce AA, Lacuara JL: In vitro parthenogenesis of mouse oocytes under 22- several experimental conditions. Zygote; 2000, 8: 45-49.
Martini AC, Molina RI, Tissera AD, Ruiz RD, Fiol De Cuneo M: Analysis of semen from patients chronically treated with low or moderate doses of aspirin-like drugs. Fertil Steril; 2003, 80: 221-222.
Matsumoto H, MA W, Smalley W, Trzaskos J, Breyer RM, Dey SK: Diversification of cyclooxygenase-2-derived prostaglandins in 25 ovulation and implantation. Biol Reprod; 2001, 64: 1557-1565.
Mayes PA: Metabolismo de los ácidos grasos insaturados y de eicosanoides. In: Murria RK, Granner DK, Mayes PA Rodwell VW. Bioquímica de Harper, El Manual Moderno, México. 1994, p269-278.
Nayak NR, Sengupta J, Ghosh D: Antinidatory effects of luteal phase administration of mifepristone (RU486) in associated with changes in endometrial prostaglandins during the implantation window. Contraception; 1998, 58: 111-117.
Orczyk GP, Behrman HR: Ovulation blockade by aspirin or indomethacin. In vivo evidence for a role of prostaglandin in gonadotropin secretion. Prostaglandins; 1972, 1: 3-20.
Ostensen P, Villiger PM: Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus. Lupus; 2001, 10: 135-139.
Ruiz RD, Fiol De Cuneo M, Santillán ME, Ponce AA, Vincenti L, Lacuara JL, Stutz G: Hypoosmotic sweeling test (HOST) for assesing the integrity of the mouse sperm membrane and its relationship with other functional parameters. Effects of 2-deoxyadenosine. J Exp Anim Sci; 1995 37: 156-164.
Sato T, Taya K, Jyujo T, Igarashi M: Ovulation block by indomethacin, an inhibitor of prostaglandin synthesis: a study of its site of action in rats. J Reprod Fert; 1974, 39: 33-40.
Scherle PA, Ma W, Lim H, Dey SK, Trzaskos JM: Regulation of cyclooxygenase-2 induction in the mouse uterus during decidualization. An event of early pregnancy. J Biol Chem; 2000, 275: 37086-37092.
Shalev J, Shemesh M, Levinshal T, Marcus S, Breitbart H: Localization of cyclooxigenase and production of prostaglandins in bovine spermatozoa. J Reprod Fertil; 1994, 101: 405-413.
Silvia WJ: Eicosanoids. In:Knobil E, Neill JD. Encyclopedia of reproduction. Academic Press, San Diego. 1998, p991-1001.
Smith G, Roberts R, Hall C, Nuki G: Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs. Br J Rheumatol; 1996, 35: 458-462.
Song H, Lim H, Das SK, Paria BC, Dey SK: Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal ephithelium correlates with implantation failure in LIF-deficient mice. Mol Endocrinol; 2000, 14: 1147-1161.
Stutz G, Martini AC, Ruiz RD, Fiol De Cuneo M, Muñoz L, Lacuara JL: Functional activity of mouse sperm was not affected by low doses of aspirin-like drugs. Arch Androl; 2000, 44: 117- 128.
Vincenti LM, Fiol De Cuneo M, Ruiz RD, Martini AC, Ponce AA: Selection of high quality subpopulation of frozen thawed bovine spermatozoa by filtration in a Sephadex column. J Exp Anim Sci; 2002, 42: 93-101.
Yanagimachi R: Mammalian fertilization. In: Knobil E, Neill JD. The physiology of reproduction. Raven Press, New York. 1994, p189-317.
Yelian FD, Dukelow WR: Effects of DNA-specific fluorochrome, Hoechst 33258 on mouse sperm motility and fertilizing capacity. Andrologia; 1992, 24: 167-170.
Yen SSC, Jaffe RB: Reproductive endocrinology: physiology, pathophysiology and clinical management. WB Sanders Company, Phyladelphia, USA, 1991.
Zanagnolo V, Dharmarajan AM, Endo K, Wallach EE: Effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, prostaglandin, and progesterone production in the rabbit. Fertil Steril; 1996, 65: 1036-1043.
Bygdeman M, Gottlieb C, Svanborg K, Swahn ML: Role of prostagalndins in human reproduction: recent advances. Adv Thromb Leukot Res; 1987, 17: 1112-1116.
Casalino SM, Linares JA, Goldraij A: Influence of underfeeding on the spontaneous contraction and on metabolism of labelled arachidonic acid in uteri isolated from intact and ovariectomized rats. Prostaglandins Leukot Essent Fatty Acids; 1996, 55: 155-158.
Clavert A, Cranz C, Bollack C: Functions of the seminal vesicle. Andrologia; 1990, 22: 185-192.
Dawood My: Nonsteroidal antiinflammatory drugs and reproduction. Am J Obstet Gynecol; 1993, 169: 1255-1265.
Duffy DM, Stouffer RL: The ovulatory gonadotrophin surge stimulates cyclooxygenase expression and prostaglandin production by the monkey follicle. Mol Hum Reprod; 2001, 7: 731-739.
Espey LL, Kohda H, Mori T, Okamura H: Rat ovarian prostaglandin levels and ovulation as indicators of the strengh of non-steroidal anti-inflammatory drugs. Prostaglandins; 1988, 36: 875-879.
Espey LL, Stein VI, Dumitrescu J: Survey of antiinflammatory agents and related drugs as inhibitors of ovulation in the rabbit. Fertil Steril; 1982, 38: 238-247.
Farr CH, Ellis LW: In vitro contractility of ratseminiferous tubules in response to prostaglandin, cyclic GMP, testosterone and 2,4-dibromoacetophenone. J Reprod Fertil; 1980, 58: 37-42.
Fiol De Cuneo, M, Ruiz RD, Ponce AA, Maldonado X, Lacuara JL: Time-related 11- changes in functional activity of mouse spermatozoa during in vitro or in vivo incubation. J Exp Anim Sci; 1994, 36: 189-200.
Fraser LR: Calciun channels play a pivotal role in the sequence of ionic change involved in initiation of mouse sperm acrosomal exocytosis. Mol Reprod Dev; 1993, 36: 368- 376.
Gurevich M, Harel-Markowitz E, Marcus S, Shore LS, Shemesh M: Prostaglandin production by the oocyte cumulus complex around the time of fertilization and the effect of prostaglandin E on the development of the early embryo. Reprod Fertil Dev; 1993, 5: 281-283.
Hayashi S, Noda Y, Mori T: Analysis of the role of prostaglandins in the fertilization process. Eur J Obstet Gynecol Reprod Biol; 1988, 29: 287-297.
Herrero MB, Franchi AM, Gimeno MAF: Mouse spermatozoa can synthesize PGE2 and 5-HETE in vitro: stimulatory action of nitric oxide. Prostaglandins Leukot Essent Fatty Acids; 1995, 53: 347-350.
Joyce CL, Nuzzo NA, Wilson L, Zaneveld LJD: Evidence for a role of cyclooxigenase (prostaglandin synthetase) and prostaglandins in sperm acrosome reaction and fertilization. J Androl; 1987, 8: 74-82.
Katz E, Dharmarajan AM, Sueoka K, Ghodganonkar RB, Dubin NH, Wallach EE: Effects of systemic administration of indomethacin on ovulation, luteinization, and steroidogenesis in the rabbit ovary. Am J Obstet Gynecol; 1989, 161: 1361-1366.
Knuth UA, Kühne J, Crosby J, Bals-Pratsch M, Kelly RW, Nieschlag E: Indomethacin and oxaprozin lower seminal prostaglandin levels but do not influence sperm motion characteristics and serum hormones of young healthy men in placebo-controlled double-blind trial. J Androl; 1989, 10: 108-119.
Löscher W, Lüttgenau H, Schlegel W, Krüger S: Pharmacokinetics of non-steroidal anti-inflammatory drugs in male rabbits after acute and chronic administration and effect of chronic treatment on seminal prostaglandins, sperm quality and fertility. J Reprod Fert; 1988, 82: 353-364.
Makler A: The improved ten-micrometer chamber for rapid sperm count and motility evaluation. Fertil Steril; 1980, 33: 337-338.
Martini AC, Fiol De Cuneo M, Ruiz RD, Ponce AA, Lacuara JL: In vitro parthenogenesis of mouse oocytes under 22- several experimental conditions. Zygote; 2000, 8: 45-49.
Martini AC, Molina RI, Tissera AD, Ruiz RD, Fiol De Cuneo M: Analysis of semen from patients chronically treated with low or moderate doses of aspirin-like drugs. Fertil Steril; 2003, 80: 221-222.
Matsumoto H, MA W, Smalley W, Trzaskos J, Breyer RM, Dey SK: Diversification of cyclooxygenase-2-derived prostaglandins in 25 ovulation and implantation. Biol Reprod; 2001, 64: 1557-1565.
Mayes PA: Metabolismo de los ácidos grasos insaturados y de eicosanoides. In: Murria RK, Granner DK, Mayes PA Rodwell VW. Bioquímica de Harper, El Manual Moderno, México. 1994, p269-278.
Nayak NR, Sengupta J, Ghosh D: Antinidatory effects of luteal phase administration of mifepristone (RU486) in associated with changes in endometrial prostaglandins during the implantation window. Contraception; 1998, 58: 111-117.
Orczyk GP, Behrman HR: Ovulation blockade by aspirin or indomethacin. In vivo evidence for a role of prostaglandin in gonadotropin secretion. Prostaglandins; 1972, 1: 3-20.
Ostensen P, Villiger PM: Nonsteroidal anti-inflammatory drugs in systemic lupus erythematosus. Lupus; 2001, 10: 135-139.
Ruiz RD, Fiol De Cuneo M, Santillán ME, Ponce AA, Vincenti L, Lacuara JL, Stutz G: Hypoosmotic sweeling test (HOST) for assesing the integrity of the mouse sperm membrane and its relationship with other functional parameters. Effects of 2-deoxyadenosine. J Exp Anim Sci; 1995 37: 156-164.
Sato T, Taya K, Jyujo T, Igarashi M: Ovulation block by indomethacin, an inhibitor of prostaglandin synthesis: a study of its site of action in rats. J Reprod Fert; 1974, 39: 33-40.
Scherle PA, Ma W, Lim H, Dey SK, Trzaskos JM: Regulation of cyclooxygenase-2 induction in the mouse uterus during decidualization. An event of early pregnancy. J Biol Chem; 2000, 275: 37086-37092.
Shalev J, Shemesh M, Levinshal T, Marcus S, Breitbart H: Localization of cyclooxigenase and production of prostaglandins in bovine spermatozoa. J Reprod Fertil; 1994, 101: 405-413.
Silvia WJ: Eicosanoids. In:Knobil E, Neill JD. Encyclopedia of reproduction. Academic Press, San Diego. 1998, p991-1001.
Smith G, Roberts R, Hall C, Nuki G: Reversible ovulatory failure associated with the development of luteinized unruptured follicles in women with inflammatory arthritis taking non-steroidal anti-inflammatory drugs. Br J Rheumatol; 1996, 35: 458-462.
Song H, Lim H, Das SK, Paria BC, Dey SK: Dysregulation of EGF family of growth factors and COX-2 in the uterus during the preattachment and attachment reactions of the blastocyst with the luminal ephithelium correlates with implantation failure in LIF-deficient mice. Mol Endocrinol; 2000, 14: 1147-1161.
Stutz G, Martini AC, Ruiz RD, Fiol De Cuneo M, Muñoz L, Lacuara JL: Functional activity of mouse sperm was not affected by low doses of aspirin-like drugs. Arch Androl; 2000, 44: 117- 128.
Vincenti LM, Fiol De Cuneo M, Ruiz RD, Martini AC, Ponce AA: Selection of high quality subpopulation of frozen thawed bovine spermatozoa by filtration in a Sephadex column. J Exp Anim Sci; 2002, 42: 93-101.
Yanagimachi R: Mammalian fertilization. In: Knobil E, Neill JD. The physiology of reproduction. Raven Press, New York. 1994, p189-317.
Yelian FD, Dukelow WR: Effects of DNA-specific fluorochrome, Hoechst 33258 on mouse sperm motility and fertilizing capacity. Andrologia; 1992, 24: 167-170.
Yen SSC, Jaffe RB: Reproductive endocrinology: physiology, pathophysiology and clinical management. WB Sanders Company, Phyladelphia, USA, 1991.
Zanagnolo V, Dharmarajan AM, Endo K, Wallach EE: Effects of acetylsalicylic acid (aspirin) and naproxen sodium (naproxen) on ovulation, prostaglandin, and progesterone production in the rabbit. Fertil Steril; 1996, 65: 1036-1043.
Downloads
Published
2020-02-18
How to Cite
1.
Martini AC, Vincenti LM, Santillán ME, Stutz G, Kaplan R, Ruiz RD, Fiol de Cuneo M. Chronic a administration of nonsteroidal - antiinflammatory drugs (NDAIDS): effects upon mouse reproductive funcions. Rev Fac Cien Med Univ Nac Cordoba [Internet]. 2020 Feb. 18 [cited 2024 Jul. 6];65(2):41-5. Available from: https://revistas.unc.edu.ar/index.php/med/article/view/27715
Issue
Section
Original Papers
License
Copyright (c) 2020 Universidad Nacional de Córdoba
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The Faculty of Medical Sciences Journal (RFCM) subscribes to the Open Access policy and does not charge authors fees for publishing, nor does it charge readers fees for accessing published articles (APC).
