Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage

Introduction: Early miscarriage is the most common complication of pregnancy and in many cases the etiology is not clearly understood. We aim to profile the expression of Mfn2 and mitochondrial damage in villous tissues, in order to determine the underlying mechanism of unexplained miscarriage. Methods: We investigated placental villous samples of 30 women with early unexplained miscarriage (miscarriage group) and 30 women with normal pregnancy (control group). Immunohistochemistry and western blotting were used to detect the Mfn2 expression. We observed trophoblastic cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels by western blotting. Transmission electron microscopy was used to analyze mitochondrial morphology and phosphomolybdic acid colorimetric method was used to measure the ATP content of all villous samples. Results: Mfn2 staining showed extra-nuclear localization in the trophoblastic cells. Compared with the control group, the levels of Mfn2 and Bcl-2 were markedly decreased (P < 0.01), while both the levels of Bax protein and apoptosis index (AI) were increased in the miscarriage group (P < 0.01). Mfn2 levels positively correlated with Bcl-2, but negatively correlated with Bax. Moreover, compared to the control group (33.8 +/- 6.5 mu mol/g), ATP levels in the miscarriage group were significantly decreased (15.8 +/- 4.8 mu mol/g). In addition, obvious impairment of mitochondrial function was observed in trophoblastic cells from the unexplained miscarriage group. Conclusion: Mitochondrial morphologic and functional changes were observed in trophoblastic cells, and in relation with apoptosis, may be correlated with low levels of Mfn2. Deficient expression of Mfn2 in trophoblastic cells could be an important cause of early miscarriage. (C) 2013 Elsevier Ltd. All rights reserved.