Normal ve Molar Gebeliklerde Endometrial Reseptivitenin Değerlendirilmesi

Abstract

Development of the placenta and fetus is a continuous process that begins at the time of fertilization. Endometrial receptivity and desidual invasion with trophoblasts are essential for succesful placentation and maintanence of a healty pregnancy. Establisment of endometrial receptivity, implantation, trophoblastic proliferation and invasion are strictly controlled with cytokines and growth factors released from maternal and fetal tissues. Leukemia inhibitory factor (LIF) and insulin like growth factor-1 (IGF-1) are two of the most important growth factors mediating trophoblast proliferation and endometrial receptivity. LIF has an important role in preimplantation blastocyst-endometrium interactions, implantation and placental development. Additionally LIF induces trophoblastic proliferation and invasion. IGF-1 plays a role in differantiation of cytotrophoblasts and migration of extravillous trophoblasts. Autophagy, also called type II programmed cell death, is an intracellular process responsible for the removal of cytoplasmic particles, organelles and long acting proteins via lysosomes. Molar pregnancies occur as a result of abnormal fertilisation and characterized by aberrant trophoblast proliferation. Trophoblasts in molar pregnancies have a tendency for local invasion and metastasis. This study aims to establish roles of LIF and IGF-1, which are two important cytokines mediating trophoblast-endometrium interactions and trophoblast proliferation, in pathophysiology of molar pregnancy. Our further aim is to identify effect of autophagy on abnormal trophoblastic proliferation. 16 molar placentas were enrolled in this study including 8 with partial mole and 8 with complete mole diagnosed histopathologically and with immunohistochemistry. Control group consisted of 8 normal first trimester placentas derived from curettage material of unwanted pregnancies. Expression of LIF, IGF-1 and beclin-1 among placental cellgroups were identified immunohistochemically. Histopathological evaluation of tissues revealed significant decidual leukocyte infiltration in complete moles suggesting an immune response against molar tissue which has completely paternal origin. LIF immunoreactivity is found to be increased in ekstravillous trophoblasts (EVT) of complete and partial moles. This led us to think LIF may be an autocrine mediator of abnormal trophoblastic proliferation and invasion. A significant decrease in decidual LIF immunoreactivity in complete and partial moles is found, suggesting a control mechanism of decidua against proliferating trophoblasts. Evaluation of beclin-1 immunoreactivity revealed a decreased immunoreaction in villous trophoblasts of complete mole placentas. We suggest this decrease in autophagy in villous trophoblasts increases trophoblast survival and contributes to enormous trophoblast population in complete molar pregnancies. However there is a decrease in beclin-1 immunoreactivity in deciduas of complete and partial molar pregnancies suggesting an decreased autophagy in decidua. Decreased autophagy of decidua may be a control mechanism against trophoblast invasion in molar pregnancies. Evaluation of IGF-1 immunoreactivity showed a decreased immunoreaction in glandular epithelium of complete molar placentas. In complete molar pregnancies characterized by aberrant trophoblastic proliferaton and invasion, this decrease in IGF-1 may be another control mechanism of decidua to limit the invasion. These findings suggest that decidual leukocyte infiltration and decreased endometrial expression of IGF-1 and LIF are efforts by decidua to limit trophoblast proliferation and invasion. LIF may be a mediator of abnormal trophoblast proliferation and invasion in molar pregnancies regulated in an autocrine fashion by EVT.