ALTERATION OF TROPHOBLASTIC TISSUE APOPTOSIS AND THEIR ROLE IN TOXOPLASMOSIS INDUCE MISCARRIAGE
Keywords:
Toxoplasma gondii, apoptosis, miscarriageAbstract
Toxoplasma gondii ( T. gondii) , a common protozoan parasite. T. gondii infection occurs worldwide and it is one of the most common infections in humans. The infection is mainly acquired by ingestion of undercooked or raw meat containing viable tissue cysts or by ingestion of food and water that is contaminated with oocysts shed by cats . In addition, it has been established that T. gondii can be transmitted from a recently infected mother to her fetus. During pregnancy the primary infection may lead to severe if not fatal complications for the fetus. These direct effects can lead to spontaneous miscarriage, stillbirth or congenital anomalies .apoptosis in villous trophoblast is increased in pregnancy complications such as Toxoplasmosis infection. From our study we found that Toxoplasma gondii downregulated apoptosis when caspase 3 and caspase 9 levels were investigated using immunohistochemistry technique . Aims of Study: So the aims of this search are to investigate the levels of Caspase 3 and Caspase 9 expression within T.gondii infected trophoblastic cells and their association with infection. Method: Fifty patients (aborted women), Their range age between (16 − 46) years, were included in this study. All patients sera were subjected to Enzyme Linked Immunosorbent Assay (ELISA) to detect specific Toxoplasma gondii IgM and IgG . In addition , trophoblastic tissues from the same patients were taken to confirm the infection of the T.gondii and to evaluate the expression of caspase 9 and caspase 3 using immunohistochemstry method. Results : Immunehiostochamical technique is more sensitive than ELISA in diagnosis of T. gondii when 18 patients were positive for Toxoplasmosis by immunohistochemistry While in ELISA only 16 patients were positive for specific anti – Toxoplasma IgM. The levels of Caspase3 and caspase 9 were downregulated in infected group. Conclusion : Caspase 9 expression and Caspase 3 expression are significantly highly decreased in women with spontaneous miscarriage in T.gondii positive group compared to patients control group indicating that Toxoplasma gondii downregulated apoptosis.References
-Karhukorpi J.(2005).Sources of Toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis. BMJ, 321:142-147.
-Ismael A. , Sekkai D., Collin C. , Bout D. and Merelece M.(2003).The MIC3gene of Toxoplasma gondii is a novel vaccine candidate against toxoplasmosis .Infec.Immun.,71(11):6222-6228.
- Yong-beom k., Jeong-kyu k. , Seung-Hwa h., Choong-Hee W., Seok-Jae L., Chang-Soo H., III-Woon J., Eun-Hwan J.,Hak-Soon K. (2001). programmed cell death in placenta ;Chungbuk med. J.,V. 11,No 2,105-116.
- Heazell A. and Crocker I. (2008). Live and Let Die-Regulation of Villous Trophoblast Apoptosis in Normal and Abnormal Pregnancies. Placenta .29: 772–783.
- NishikawaY., Makala L., Otsuka H., Mikami T. and Nagasawa H. . (2002). Mechanisms of apoptosis in murine fibroblasts by two intracellular protozoan parasites, Toxoplasma gondii and Neospora caninum . Parasite Immunol; 24: 347-354.
- Ringler G. and Strauss J. (1990).III. In vitro systems for the study of human placental endocrine function. Endocr. Rev., 11: 105-123.
- Goodsell D. ( 2000). The molecular perspective: caspases. The Oncologist, 5: 435-436.
- World Health Organization (2003): Basic Laboratory Procedures in Clinical Samples, 2nd.
- Remington J., Mcleod R., Thulliez P., and Desmonts G. (2001). Toxoplasmosis In: Remington JS and Klein JO (Eds). Infectious Diseases of the Fetus and Newborn Infant. 5thed. Philadelphia: WB Saunders.; 205-346.
- Goldspy R., Kindt T., Osborne B. (2000) .In Kuby immunology 4th ed. New York: WH Freeman and company.
- Salman L. (2006) .Correlation between apoptosis and Toxoplasma in abortion induction: relevance of TUNEL assay and caspases, M. Sc. Thesis. Coll. Med., Univ. AL-Nahrain.
- Nash J., Chissel S., Jones J., Warburton F., Verlander N. (2005) . Risk factors for toxoplasmosis in pregnant women in Kent, United Kingdom. Epidemiol. Infect., 133:475-483.
- Pan G., Humke E. and Dixit V. (1998). Activation of caspases triggered by cytochrome c in vitro. FEBS Lett. 426, 151-154.
- Goebel S., Lüder C. and Gross U.(2001). Inhibition of host cell apoptosis by Toxoplasma gondii is accompanied by reduced activation of the Caspase cascade and alterations of poly(ADP-ribose) polymerase reaction .J.Cell.Sce. , 114, 3495-3505.
- Goebel S., Lüder C. and Gross U. (1999). Invasion by Toxoplasma gondii protects human-derived HL-60 cells from actinomycin D-induced apoptosis. Med. Microbiol. Immunol. 187, 221-226.
- Dobrowolski J. and Sibley L. (1996). Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Cell, 84: 933-939.
