Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model.
BACKGROUND
This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin.


METHODS
Forty young female mice were divided randomly into two groups. The first was the treatment group intraperitoneally administered cisplatin (1.5mg/kg). The untreated control group was likewise injected with physiological saline for 10 days. One month later, we observed the ovarian weight and morphological changes, particularly the development of follicles and concentration of sex hormones. Immunohistochemistry and western blotting were used to measure the two groups. We later evaluated ovarian cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels. We used transmission electron microscopy in order to observe the ultrastructure of ovarian cells. The phosphomolybdic acid colorimetric method was used to measure the ATP content in the ovarian tissue. Finally, the mitochondrial membrane potential of ovarian cells was detected with JC-1 dye.


RESULTS
The cisplatin resulted in a decline of body weight, reduced ovarian weight significantly, and resulted in disorders of the extrous cycle. The follicles' number decreased within the tissue's stromal hyperplasia. Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed. However, Mfn2 was present in the cell's cytoplasm in both groups. Nevertheless, the Mfn2 levels and the expression of Bcl-2 were significantly decreased (p<0.05), but the expression of Bax and the apoptosis index (AI) was increased. In addition, the ATP levels (35.2 ± 5.7 μmol/g) of the control group were significantly higher (13.5 ± 3.8 μmol/g). Lastly, an obvious impairment of mitochondrial function and structure was observed.


CONCLUSIONS
The intreperitoneal injection of cisplatin, when administered for 10 days, establishes a POF model. Thus, the above results suggest that lower expression of Mfn2 may be involved in the mechanism of premature ovarian failure by affecting both the mitochondria's energy metabolism and its apoptosis. This decides the termination of the follicles' development.
Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Wenqi
W
Chen
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Xiaoyan
X
Xu
Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Lingjuan
L
Wang
Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Ge
G
Bai
Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Wenpei
W
Xiang
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D020558:GTP Phosphohydrolases / Q000172:deficiency / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000502:physiology*; D010053:Ovary / Q000378:metabolism / Q000503:physiopathology* / Q000648:ultrastructure; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction
D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse; D002945:Cisplatin