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Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model.

Chen W, Xu X, Wang L, Bai G, Xiang W - PLoS ONE (2015)

Bottom Line: The follicles' number decreased within the tissue's stromal hyperplasia.Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed.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.

View Article: PubMed Central - PubMed

Affiliation: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

ABSTRACT

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.

Method: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Morphologic change in ovarian tissues and hormone levels of the two groups.A: Morphology of ovarian tissues was determined by use of HE staining in both the control group and the cisplatin group (blue nuclei, red cytoplasm); B: Comparison of the ovarian weights; C: The comparison of hormone levels (FSH, Estradiol). *P<0.05 vs control group.
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pone.0136421.g001: Morphologic change in ovarian tissues and hormone levels of the two groups.A: Morphology of ovarian tissues was determined by use of HE staining in both the control group and the cisplatin group (blue nuclei, red cytoplasm); B: Comparison of the ovarian weights; C: The comparison of hormone levels (FSH, Estradiol). *P<0.05 vs control group.

Mentions: For detecting the correlation between Mfn2 and POF, we established a POF model in mice. The results show that cisplatin decreased the mice’s body weight, disrupted the estrous cycle, and significantly reduced ovarian weight (Fig 1B). We also noticed that within the ovarian tissues of the cisplatin group, there appeared stromal hyperplasia, antral follicle, and preantral follicles (Fig 1A). This of course differed from the control groups. Low levels of estradiol and elevated gonadotropin levels were observed in cisplatin groups (Fig 1C).


Low Expression of Mfn2 Is Associated with Mitochondrial Damage and Apoptosis of Ovarian Tissues in the Premature Ovarian Failure Model.

Chen W, Xu X, Wang L, Bai G, Xiang W - PLoS ONE (2015)

Morphologic change in ovarian tissues and hormone levels of the two groups.A: Morphology of ovarian tissues was determined by use of HE staining in both the control group and the cisplatin group (blue nuclei, red cytoplasm); B: Comparison of the ovarian weights; C: The comparison of hormone levels (FSH, Estradiol). *P<0.05 vs control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556514&req=5

pone.0136421.g001: Morphologic change in ovarian tissues and hormone levels of the two groups.A: Morphology of ovarian tissues was determined by use of HE staining in both the control group and the cisplatin group (blue nuclei, red cytoplasm); B: Comparison of the ovarian weights; C: The comparison of hormone levels (FSH, Estradiol). *P<0.05 vs control group.
Mentions: For detecting the correlation between Mfn2 and POF, we established a POF model in mice. The results show that cisplatin decreased the mice’s body weight, disrupted the estrous cycle, and significantly reduced ovarian weight (Fig 1B). We also noticed that within the ovarian tissues of the cisplatin group, there appeared stromal hyperplasia, antral follicle, and preantral follicles (Fig 1A). This of course differed from the control groups. Low levels of estradiol and elevated gonadotropin levels were observed in cisplatin groups (Fig 1C).

Bottom Line: The follicles' number decreased within the tissue's stromal hyperplasia.Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed.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.

View Article: PubMed Central - PubMed

Affiliation: Family Planning Research Institute, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

ABSTRACT

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.

Method: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus