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Cytotec Induced Embryotoxicity in Developing Mus musculus

  • Naeem, Khadija ;
  • Ahmad, Naveed ;
  • Asmatullah, Asmatullah
  • Received : 2009.12.24
  • Accepted : 2010.03.10
  • Published : 2010.10.01

Abstract

The study was carried out to assess the developmental abnormalities induced by Cytotec in mice during intrauterine life. Pregnant mice were exposed to a single dose of 0, 0.02, 0.04, 0.06, 0.08 and $0.1{\mu}g$/g BW on day 8 of gestation. Fetuses were recovered on day 18 of gestation. These fetuses were subjected to morphological and morphometric studies. Morphological studies showed abnormalities like anophthalmia, microophthalmia, micromelia and syndactyly. In addition to these, resorptions were also encountered in the higher dose groups. Morphometric analysis showed an overall reduction in body weight, crown rump length, brain and eye circumference, pinna and snout size, length of fore and hind limb and tail size with a significant difference (p<0.001) compared to controls. The outcomes of histological studies revealed some brain defects like hydrocephaly, enlarged third ventricle and undifferentiated ectoneural cells and abnormalities of the heart included right auricle thrombosis and degeneration of trabecular zone.

Keywords

Cytotec;Embryotoxicity;Developmental Anomalies;Mice

References

  1. Adair, C. D. and D. F. Lewis. 1998. Labor induction with oral versus vaginal misoprostol: a randomized double-blind trial. Am. J. Obstet. Gynecol. 92:810-813. https://doi.org/10.1016/S0029-7844(98)00278-6
  2. Al-Hussaini, T. 2001. Uterine rupture in second trimester abortion in a grand multiparous woman: A complication of misoprostol and oxytocin. Eur. J. Obstet. Gynecol. Rerpod. Biol. 96(2):218-219. https://doi.org/10.1016/S0301-2115(00)00445-0
  3. Andolina, K. L., J. E. Tolosa, J. M. Monzo, N. S. Roberts and S. Daly. 2003. Oral misoprostol is rapidly absorbed in postpartum women at term. J. Matern. Fetal Neonatal. Med. 14:229-232. https://doi.org/10.1080/jmf.14.4.229.232
  4. Berghahn, L., D. Christensen and S. Droste. 2001. Uterine rupture during second trimester abortion associated with misoprostol. Obstet. Gynecol. 98:976-977. https://doi.org/10.1016/S0029-7844(01)01546-0
  5. Carbonell, J. L. L., J. Rodriguez, E. Delagdo, C. Sanchez, F. Vargas, L. Valera, J. Mari, F. Valero, I. Salvador and M. Llorente. 2004. Vaginal misoprostol 800 ${\mu}g$ every 12 h for second-trimester abortion. Contraception 70:55-60. https://doi.org/10.1016/j.contraception.2004.01.010
  6. Carlan, S. J., D. Blust and W. F. O'Brien. 2002. Buccal versus intravaginal misoprostol administration for cervical ripening. Am. J. Obstet. Gynecol. 186:229-233. https://doi.org/10.1067/mob.2002.119630
  7. Castleman, L. D., K. T. Oanh, A. G. Hyman, T. Thuy le and B. D.Blumenthal. 2006. Introduction of the dilation and evacuation procedure for second-trimester abortion in Vietnam using manual vacuum aspiration and buccal misoprostol. Contraception 74:272-276. https://doi.org/10.1016/j.contraception.2006.03.021
  8. Coelho, K.-E. F. A., M. V. F. Barmento, C. M. Veiga, C. E. Speck-Martins, H. P. N. Safattle, C. V. Castro and N. Niikawa. 2000. Misoprostol embryotoxicity: Clinical evaluation of fifteen patients with arthrogryposis. Am. J. Med. Genet. 95(4):297-301. https://doi.org/10.1002/1096-8628(20001211)95:4<297::AID-AJMG1>3.0.CO;2-K
  9. Collins, P. W. 1990. Misoprostol: discovery, development and clinical applications. Med. Res. Rev. 10:149-172. https://doi.org/10.1002/med.2610100202
  10. CSGN, 2006. http://www.csgnetwork.com/glossary/html#calculator
  11. Dal Pizzol, T. S., F. P. Knop and S. S. Mengue. 2006. Prenatal exposure to misoprostol and congenital anomalies: systematic review and meta analysis. Reprod. Toxicol. 22:666-671. https://doi.org/10.1016/j.reprotox.2006.03.015
  12. Dal Pizzol, T. S., M. T. V. Sanseverino and S. S. Mengue. 2008. Exposure to misoprostol and hormones during pregnancy and risk of congenital anomalies. Cad. Saude. Publica 24(6):1447-1453. https://doi.org/10.1590/S0102-311X2008000600025
  13. Deraedt, R., B. Vannier and R. Fournex. 1985. Toxicological study on RU 486. In: The antiprogestin steroid RU 486 and human fertility control (Ed. E. E. Baulieu and S. J. Segal). New York, Plenum Press. pp. 123-126.
  14. Derman, R. J., B. S. Kodkany, S. S. Goudar, S. E. Geller, V. A.Naik, M. B. Bellad, S. Patted, A. Patel, S. Edlavitch and T. Hartwell. 2006. Oral misoprostol in preventing postpartum hemorrhage in resource-poor communities: a randomized controlled trial. Lancet 368:1248-1253. https://doi.org/10.1016/S0140-6736(06)69522-6
  15. El-Rafaey, H., D. Rajasekar, M. Abdalla, L. Calder and A. Templeton. 1995. Induction of abortion with mifepristone (RU 486) and oral and vaginal misoprostol. N. Eng. J. Med., 332:983-987. https://doi.org/10.1056/NEJM199504133321502
  16. Foote, E. F., D. R. Lee, A. Karim, W. F. Keane and C. E.Halstenson. 1995. Disposition of misoprostol and its active metabolite inpatients with normal and impaired renal function. J. Clin. Pharmacol. 35:384-389. https://doi.org/10.1002/j.1552-4604.1995.tb04078.x
  17. Ginath, S. and H. Zakut. 2001. Misoprostol-for cervical ripening? Eur. J. Obstet. Gynecol. Reprod. Biol. 99:152-153. https://doi.org/10.1016/S0301-2115(01)00413-4
  18. Goldberg, A. B., B. S. Greenberg and P. D. Darney. 2001. Misoprostol and pregnancy. N. Eng. J. Med. 343:38-48.
  19. Gonzalez, C. H., M. J. Marques-Dias, C. A. Kim, S. M. Sugayama,J. A. Dal pizzol, S. M. Huson and L. D. Holmes. 1998. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet, 351(9116):1624-1627. https://doi.org/10.1016/S0140-6736(97)12363-7
  20. Henriques, A., A. V. Lourenco, A. Riberiniho, H. Ferreira and L. M. Graca. 2007. Maternal death relate to misoprostol overdose. Obstet. Gynecol. 109:489-490. https://doi.org/10.1097/01.AOG.0000253248.64065.94
  21. Gonzalez, C. H., F. R. Vargas, A. B. Perez, C. A. Kim, D. M. J.Brunoni, Marques-Dias, C. R. Leone, J. Correa Neto, J. C.Llerena and J. C. de Almaida. 1993. Limb deficiency with or without mobius sequence in seven Brazilian children associated with misoprostol use in the first trimester of pregnancy. Am. J. Med. Genet. 47(1):59-64. https://doi.org/10.1002/ajmg.1320470113
  22. Hemminki, E., T. Luostarinen, E. Pukkala, D. Apter and T. Kakulinen. 2002. Oral contraceptive use before first birth and risk of breast cancer: a case control study. BMC Women’s Health 2:9. https://doi.org/10.1186/1472-6874-2-9
  23. Ho, P. C., S. W., Ngai, K. L. Liu, G. C. Wing and S. W. Lee. 1997.Vaginal misoprostol compared with oral misoprostol in termination of second trimester pregnancy. Obstet. Gynecol. 90:735-738. https://doi.org/10.1016/S0029-7844(97)00419-5
  24. Javed, L., M. Maik, N. Jamal, S. Sheikh and F. Farzana. 2004. Mid-trimester termination of pregnancy-comparison of sublingual with vaginal misoprostol. Biomedica 20:56-59.
  25. Jonakait, G. M. and L. Ni. 2009. Progstaglandins compromise basal forebrain cholinergic neuron differentiation and survival: action at EP 1/3 receptors result in AIF induced death. Brain Res. 1285:30-41. https://doi.org/10.1016/j.brainres.2009.06.037
  26. Jost, A. 1986. New data on the hormonal requirements of the pregnant rabbit: partial pregnancies and fetal abnormalities\ after treatment with a hormonal antagonist at subabortifacient doses. C. R. Acad. Sci. 303(Series III NO. 7):281-284.
  27. Khan, R. and H. El-Rafaey. 2003. Pharmacokinetics and adverse effects profile of rectally administered misoprostol in the third stage of labor. Obstet. Gynecol. 101:968-974. https://doi.org/10.1016/S0029-7844(03)00174-1
  28. McEvoy, G. K. 1996. American hospital formulatory service-drug information 96. Bathesda, MD: American Society of Health System Pharmacist Inc. (Plus supplements). p. 2171.
  29. Meckstroth, K. R., A. K. Whitaker, S. Bertisch, A. B. Goldberg and P. D. Darney. 2005. Misoprostol administered through epithelial route. Obstet. Gynecol. 108:82-90.
  30. Middleton, T., E. Schaff, S. L. Fielding, M. Scahill, C. Shannon, E.Westheimer, T. Wilkinson and B. Winikoff. 2005. Randomized trial of mifepristone and buccal or vaginal menstrual period. Contraception 72:328-332. https://doi.org/10.1016/j.contraception.2005.05.017
  31. Nopdonrattakoon, L. 2003. A comparison for labor induction: a randomized controlled trial. J. Obstet. Gynecol. Res. 29:87-91. https://doi.org/10.1046/j.1341-8076.2003.00084.x
  32. Norman, J. E., K. J. Thong and D. T. Baird. 1991. Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifepristone. Lancet 338:1233-1236. https://doi.org/10.1016/0140-6736(91)92102-8
  33. Paungmora, N., Y. Herabutya, P. Prasertsawat and P. Punyavachira. 2004. Comparison of oral and vaginal misoprostol for induction of labor at term: a randomized controlled trial. J. Obstet. Gynecol. Res. 30:358-362. https://doi.org/10.1111/j.1447-0756.2004.00215.x
  34. Product Information. 2009. $Cytotect^{\circledR}$. Pfizer Australia Private, Limited.
  35. Product Information. 2005. $Cytotect^{\circledR}$. Pfizer Inc. New York.
  36. Qazi, R. A. 2006. Congenital anomalies associated with failed misoprostol termination of pregnancy. J. Liaquat Uni. Med. Health Sci. 5(3):122-124.
  37. Robert, A., J. E. Nezamis and J. P. Phillips. 1967. Inhibition of gastric secretions by prostaglandins. Am. J. Dig. Sci. 12:1073-1076. https://doi.org/10.1007/BF02233268
  38. Rozenberg, P., S. Chevret, F. Goffinet, I. Durand, Y. Ville, C.Vayssiere, A. Roberto, Z. Lahna, I. Nisand, C. Fisch, P. Chaumet-Riffaud and C. Chastang. 2001. Induction of labor with a viable infant: a randomized clinical trial comparing intra-vaginal dinoprostone. Br. J. Obstet. Gynecol. 108:1256-1262.
  39. Shetty, A., P. Danielian and A. Temleton. 2002. Sublingual compared with oral misoprostol in term labor induction: a randomized controlled trial. Br. J. Obstet. Gynecol. 109:645-650. https://doi.org/10.1111/j.1471-0528.2002.01459.x
  40. Shetty, A., I. Livingstone, S. Acharya, P. Rice, P. Danielian and A. Templeton. 2003. Oral misoprostol (100 ${\mu}g$) versus vaginal misoprostol (25 ${\mu}g$) in term labor induction: a randomized comparison. Acta. Obstet. Gynecol. Scand. 82:1103-1106. https://doi.org/10.1046/j.1600-0412.2003.00246.x
  41. Song, J. 2000. Use of misoprostol in obstetrics and gynecology. Obstet. Gynecol. Surv. 55:503-510. https://doi.org/10.1097/00006254-200008000-00023
  42. Tang, O. S., H. Schweer, H. W. Seyberth, S. W. Lee and P. C. Ho. 2002. Pharmacokinetics of different routes of misoprostol. Hum. Reprod. 17:332-336. https://doi.org/10.1093/humrep/17.2.332
  43. Uzumcu, A., B. Karaman, G. Toksoy, Z. O. Uyguner, S. Candan, H.Eris, B. Tatli, B. Gechinli, A. Yuksel, H. Kayserili and S.Basaran. 2009. Molecular genetic screening of MBS1 locus on chromosome 13 for microdeletions and exclusion of FGF9, GSH1 and CDX2 as causative genes in patients with Mobius Sybdrome. Eur. J. Med. Genet. 52(5):315-320. https://doi.org/10.1016/j.ejmg.2009.05.003
  44. Zieman, M., S. K. Fong, N. L. Benowitz, D. Banskter and P. D. Darney. 1997. Absorption kinetics of misoprostol with oral or vaginal administration. Obstet. Gynecol. 90:88-92. https://doi.org/10.1016/S0029-7844(97)00111-7