Kadmiyumun gebeliğin farklı dönemlerindeki sıçan plasentalarında bulunan trofoblast hücre proliferasyonu ve apoptozisi üzerine etkisi
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Dosyalar
Tarih
2013
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Yayıncı
Trakya Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Plasenta, anne ile fetüs arasındaki birçok metabolik aktiviteyi düzenleyen bir geçiş bölgesidir ve gebeliğin sonucunu etkileyen kritik bir organdır. Embriyonunun sağlıklı bir şekilde gelişebilmesi için plasental gelişimin tam olması gerekir. Nitekim erken embriyonik ölümlerin en büyük nedenlerinden birisi de anormal plasental gelişimlerdir. Bu çalışmada, gebeliğin farklı günlerinde kadmiyumun plasentadaki trofoblast proliferasyonu ve differensiyasyonu ile apoptotik aktiviteyi nasıl etkilediğini, dolayısıyla plasental gelişim üzerine olan etkilerini immünohistokimyasal ve TUNEL teknikleriyle göstermeyi amaçladık. Çalışmamızda deney modeli, kontrol ve kadmiyum grubu olmak üzere plasental gelişimin gerçekleştiği gebeliğin 15, 17, 19 ve 21. günlerinden oluşmaktaydı. Kadmiyum grubundaki dişi sıçanlara gebeliğin başlangıcından sakrifiye edilecekleri zamana kadar olmak üzere 0,5 mg/kg kadmiyum (2 ml sodyum klorür içerisinde çözünerek) günlük tek doz olarak subkutan yoldan verildi. Gebe dişilerin plasental gelişimin gerçekleştiği gebeliğin 15, 17, 19 ve 21. günlerinde embriyo ve plasentaları ayrı ayrı alındı ve alınan plasentalar mikroskobik incelemeler için işlemlendirildi. Gebeliğin 15. günündeki kontrol grubu plasentalarda tüm katmanların oluşmuş olduğu gözlendi ve bu günden sonra da plasentanın devamlı bir büyüme içerisinde olduğu görüldü. Kadmiyum grubunda da 15. günden itibaren plasentada tüm katmanların varlığı gözlendi. Ancak boyut olarak kontrol grubuna göre daha küçük olduğu gözlendi. Özellikle bağlantı zonundaki küçülme dikkat çekiciydi. Kadmiyum grubu labirent tabakasında düzensizlikler ve kan damarlarında genişleme görüldü. Glikojen hücre sayısında ise 15. günden sonra kontrol grubuna göre bir azalma izlendi. Kadmiyuma bağlı olarak plasentada tüm gebelik günlerinde prolifere hücre nükleer antijen pozitif hücre sıklığının azalma gösterdiği, apoptotik hücre sayısının ise arttığı saptandı. Sonuç olarak; gebelik boyunca verilen kadmiyumun plasentanın normal yapısını bozduğu, trofoblast proliferasyonunu engellediği ve apoptotik trofoblast hücre sayısını da arttırarak anormal plasental gelişime sebebiyet verdiği tespit edildi.
Abstract
Placenta is a transition area regulating many metabolic activities between the mother and fetus and a critical organ influencing the outcome of pregnancy. Placental development must be completed in order the embryo to develop in a healthy way. Indeed, one of the biggest causes of early embryonic death is abnormal development of the placenta. In this study, we aimed to show how cadmium affects the trophoblast proliferation and differentiation in the placenta and the apoptotic activity in different gestational days and hence, its effects of the placental development with immunohistochemical and TUNEL techniques. Experimental model of our study consisted of placental development of control and cadmium groups on 15, 17, 19 and 21th days of the gestation. Female rats in cadmium groups were subcutaneously administered a single dose of 0.5 mg cadmium/kg/d dissolved in sodium chloride as 2 mL/kg cadmium chloride until the day they sacrificed. Embryo and placenta of the female rats were seperately removed on 15, 17, 19 and 21th days of the gestation in which the placental development takes place and the placentas were processed for microscopic examinations. In the placentas of the control group, all the layers were observed to be formed on the 15th gestational day and thereafter a continuous growth was monitored. In cadmium group also all the layers were existed from the 15th gestational day. However they were smaller in size than the controls. It was noteworthy especially the reduction in the connection zone. In the cadmium group, irregularities in the labyrinth layer and dilation of the blood vessels were observed. The number of glycogen cells were significantly decreased after the 15th day compared to the controls. Frequency of proliferating cell nuclear antigen positive cells was decreased and the number of apoptotic cells was increased in all the gestational days related to cadmium. In conclusion; cadmium administered during the pregnancy was observed to cause abnormal placental development by disrupting the normal structure of placenta, inhibiting the proliferation of trophoblast and increasing the number of apoptotic trophoblast cells.
Abstract
Placenta is a transition area regulating many metabolic activities between the mother and fetus and a critical organ influencing the outcome of pregnancy. Placental development must be completed in order the embryo to develop in a healthy way. Indeed, one of the biggest causes of early embryonic death is abnormal development of the placenta. In this study, we aimed to show how cadmium affects the trophoblast proliferation and differentiation in the placenta and the apoptotic activity in different gestational days and hence, its effects of the placental development with immunohistochemical and TUNEL techniques. Experimental model of our study consisted of placental development of control and cadmium groups on 15, 17, 19 and 21th days of the gestation. Female rats in cadmium groups were subcutaneously administered a single dose of 0.5 mg cadmium/kg/d dissolved in sodium chloride as 2 mL/kg cadmium chloride until the day they sacrificed. Embryo and placenta of the female rats were seperately removed on 15, 17, 19 and 21th days of the gestation in which the placental development takes place and the placentas were processed for microscopic examinations. In the placentas of the control group, all the layers were observed to be formed on the 15th gestational day and thereafter a continuous growth was monitored. In cadmium group also all the layers were existed from the 15th gestational day. However they were smaller in size than the controls. It was noteworthy especially the reduction in the connection zone. In the cadmium group, irregularities in the labyrinth layer and dilation of the blood vessels were observed. The number of glycogen cells were significantly decreased after the 15th day compared to the controls. Frequency of proliferating cell nuclear antigen positive cells was decreased and the number of apoptotic cells was increased in all the gestational days related to cadmium. In conclusion; cadmium administered during the pregnancy was observed to cause abnormal placental development by disrupting the normal structure of placenta, inhibiting the proliferation of trophoblast and increasing the number of apoptotic trophoblast cells.
Açıklama
Doktora Tezi
Anahtar Kelimeler
Trofoblast, Sıçan, PCNA, Kadmiyum, Plasental Gelişim, Apoptozis