Evaluation of the Teratogenic Effects of the Antidepressant Drug Sertraline on Fetuses of Albino Rats

Abd El Wahab El Ghareeb, Abd El Hakim Saad, Heba Abd El Rahman, Nouf Bader Alduweesh

Abstract


Teratogenesis refers to the production of defects in the fetus. A teratogenic agent is responsible for producing such a defect. The term teratogen usually is cited in the context of causing anatomical defects in an embryo that was previously differentiating normally.
Sertraline is an often used antidepressant drug; however insufficient information is available regarding its safety during pregnancy. Therefore, this work was initiated to study the effect of prenatal exposure of mirtazapine (Sertraline) on fetuses of rats. The study was conducted on pregnant rats to observe the safety profile of sertraline in comparison to control. Pregnant albino rats (Rattus norvegicus) were administrated during organogenesis period with therapeutic dose. Fetuses were removed from the uterus and evaluated for mortality rate, growth parameters, morphological and skeletal malformation as well as histological study of liver, kidney and brain. Results showed significant reduction in placental weight of pregnant rats treated with sertraline. Treated group showed incidence of pregnancy loss and abortion. Fetal growth retardation during gestational period was recorded also some skeletal anomalies were observed, these abnormalities included weak ossification of the skull bones roof and bones forming girdles and limbs. Histopathological studies of fetuses during gestation revealed changes in liver histology such as presence of clumping of the hepatocytes with hyperchromatic nuclei and an increase in the number of megakaryocytes, kidney tissue revealed numbers of mitotic activity in the nuclei of the tubular lining epithelium and coagulative necrosis in the lining tubular epithelium of the proximal convoluted tubules at the cortex. The cerebrum showed ill developed wall of the blood vessels also the matrix of striatum in cerebrum showed vacuolization and neuronal cells in the substantia nigra showed degeneration with loss of the cytoplasmic granules. Our findings suggest the need for great caution to handle sertraline especially during pregnancy.

 


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• Andersson L., Sundstrom-Poromaa I., Bixo M., Wulff M., Bondestam K. and aStrom M. (2003): Point prevalence of psychiatric disorders during the second trimester of pregnancy: a population-based study. Am. J. Obstet. Gynecol., 189:148–154.

• Bancroft, J.D. and Gamble, M. (2002): Theory and practice of histological techniques. 5th ed. Churchill Livingstone: London, UK.

• Bellantuono C., Migliarese G. and Imperadore G.(2006): Pharmacologic therapy of depression during pregnancy. RecentiProg Med., 97(2): 94-107.

• Bonari L., Pinto N., Ahn E., Einarson A., Steiner M. and Koren G. (2004): Perinatal risks of untreated depression during pregnancy. Can. J. Psychiatry, 49: 726–735.

• Camacho R.S., Cantinelli F.S., Ribeiro C.S., Cantilino A., Gonsales B.K., Braguittoni E. and RennoJr.R.(2006): Psychiatry disorders in pregnancy and puerperium: classification, diagnosis and treatment. Rev PsiquiatrClin.,33(2):92-102.

• Deinz, E., Dural, K. and Tuncay, P. (1995): Visualization of the fetal skeletal system by double staining with alizarin red and alcian blue. Gazi Medical Journal, 6:55-58.

• El Marroun H., Jaddoe V.W., Hudziak J.J., Roza S.J., Steegers E.A., Hofman A., Verhulst FC., White TJ., Stricker BH. andTiemeier H. (2012): Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch. Gen. Psychiatry, 69:706–714.

• Farris, EJ. (Ed.). The care and breeding of laboratory animals. 7 ed. New York: John Willey and Sons, 1967.

• Gorman L.L., O'Hara M.W., Figueiredo B., Hayes S., Jacquemain F., Kammerer M.H., Klier C.M., Rosi S., Seneviratne G. andSutter-Dallay AL; TCS-PND Group. (2004): Adaptation of the structured clinical interview for DSM-IV disorders for assessing depression in women during pregnancy and post-partum across countries and cultures. Br. J. Psychiatry. Suppl. 46:s17–s23.

• Heikkinen T., Ekblad U., Palo P. and Laine K. (2003): Pharmacokinetics of fluoxetine and norfluoxetine in pregnancy and lactation. Clin.Pharmacol.Ther., 73:330–337.

• Jablensky A.V., Morgan V., Zubrick S.R., Bower C. and Yellachich L.A. (2005): Pregnancy, delivery, and neonatal complications in a population cohort of women with schizophrenia and major affective disorders. Am. J. Psychiatry, 162:79–9.

• Jasmita S., Ashok K.P. and Nibha M. (2010):Behavioral and Developmental Changes in Rats with Prenatal Exposure of Mirtazapine.Sci Pharm., 78: 451–463.

• Kurki T., Hiilesmaa V., Raitasalo R., Mattila H. and Ylikorkala O. (2000): Depression and anxiety in early pregnancy and risk for preeclampsia. Obstet. Gynecol., 95:487–490.

• Lisboa S.F., Oliveira P.E., Costa L.C., Venancio E.J. and Moreira E.G.(2007): Behavioral evaluation of male and female mice pups exposed to fluoxetine during pregnancy and lactation. Pharmacology,80(1):49-56.

• Marcela R. and María E.L.(2010): Antibiotic Treatment of Dogs and Cats during Pregnancy. Veterinary Medicine International, 2010.

• McClain, R.M. and Becker, B.A. (1975): Teratogenicity, foetal toxicity and placental transfer of lead nitrate in rats. Toxicol. Appl. Pharmacol., 931: 72-82.

• Melville J.L., Gavin A., Guo Y., Fan M.Y. and Katon W.J. (2010): Depressive disorders during pregnancy: prevalence and risk factors in a large urban sample. Obstet. Gynecol., 116:1064–1070.

• Miller L.J. and LaRusso E.M. (2011): Preventing postpartum depression. Psychiatr.Clin. North Am., 34:53–65.

• Moore, KL.The developing human. 4 ed. Philadelphia: WBSaunder, 1988.

• Noorlander C.W., Ververs F.F., Nikkels P.G., van Echteld C.J., Visser G. H. and Smidt M.P. (2008): Modulation of serotonin transporter function during fetal development causes dilated heart cardiomyopathy and lifelong behavioral abnormalities. PLoS ONE 3:e2782.

• Olivier, J. D. A., Åkerud, H., Kaihola, H., Pawluski, J.L., Skalkidou, A.,Högberg, U. and Sundström-Poromaa, I. (2013):The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring. Front Cell Neurosci., 7:73.

• O’Rahilly, R.(2001): Human Embryology & Teratology, Wiley-Liss,New York, NY, USA, 3rd edition.

• Orr S.T. and Miller C.A. (1995): Maternal depressive symptoms and the risk of poor pregnancy outcome. Review of the literature and preliminary findings. Epidemiol. Rev., 17:165–171.

• Patkar A.A., Bilal L., Masand P.S. (2004): Pharmacotherapy of depression in pregnancy. Ann. Clin. Psychiatry, 16:87–100.

• Sadler, T.W.(2000): (Ed.). Langman’s medical embryology. 8 ed. Baltimore: Williams and Wilkins.

• Snell, G.D.(1956): Biology of the laboratory Mouse, 5thed. The Blakiston Company, pholadeliphia.

• Somer, GF. (1962): Thalidomide and congenital abnormalities. Lancet., 1: 912-913.

• Ververs T., Kaasenbrood H., Visser G., Schobben F., de Jong-van den Berg L. and Egberts T. (2006): Prevalence and patterns of antidepressant drug use during pregnancy. Eur. J. Clin. Pharmacol., 62:863–870.

• Weissman M.M., Pilowsky D.J., Wickramaratne P.J., Talati A., Wisniewski S.R., Fava M., Hughes C.W., Garber J., Malloy E., King C.A., Cerda G., Sood A.B., Alpert J.E., Trivedi M.H. andRush AJ; STAR*D-Child Team. (2006): Remissions in maternal depression and child psychopathology: a STAR*D-child report. JAMA 295, 1389–1398.

• Wisner K.L., Sit D.K., Hanusa B.H., Moses-Kolko E.L., Bogen D.L., Hunker D.F., Perel J.M., Jones-Ivy S., Bodnar L.M. andSinger L.T. (2009): Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am. J. Psychiatry, 166:557–566.

• Zinga D., Phillips S.D. and Born L. (2005): Postpartum depression: we know the risks, can it be prevented? Rev Bras Psiquiatr., 27 (2):56-64.


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