The influencing mechanism of mTOR signal pathway mediated by mitofusin-2 in development of follicle

OBJECTIVE: To investigate the influencing mechanism of mammalian target of rapamycin (mTOR) signal pathway mediated by mitofusin-2 (Mfn2) in the development of follicle.

MATERIALS AND METHODS: We selected 20 healthy Sprague Dawley (SD) female rats aging between 6 and 8 weeks were divided into the control group and the polycystic ovarian syndrome (PCOS) model group. Rats in PCOS group received the lavage using 0.4 mL 1% carboxymethyl cellulose solution containing letrozole (1 mg/kg/d) consecutively for 20 to 25d. We compared the body weight and ovary weight of rats, and detected levels of sera E2, T, P, FSH and LH through RIA measurement. We also observed the histological morphology of ovary through hematoxylin eosin (HE) staining, as well as the positive expression and location of rMfn2 through immunohistochemistry staining. Finally, we detected the expressions of mTOR, p-Akt, β-catenin, caspase-3, Bcl-2 and Bax in Mfn2 and mTOR signal pathways in the tissues through RT-PCR and Western blot assay.

RESULTS: In the PCOS group, the body weight of rats was lower than that of the control group, but the ovary weight of rats was higher than that in the control group. The levels of T and LH in serum were elevated, the levels of E2, P and FSH were decreased (p < 0.05). In the model group, typical polycystic changes were observed in the rats under the microscope, but no corpus luteum was observed, and a significant decrease was identified in the layers of the granular cell of the follicle. Mfn2 was widely expressed in the granular cells of the ovary, follicular fluid, inner theca cells, corpus luteum, and ovarian stroma. However, the expression in the outer theca cells was relatively low. In the observation group, the positive expression rate of Mfn2 was significantly lower (p < 0.05) than that in the control group. In the PCOS group, the mRNA and protein relative expression levels of mTOR, p-Akt, β-catenin, and Bcl-2 were significantly lower (p < 0.05) than those in the control group. Conversely, the levels of caspase-3 and Bax were significantly higher (p < 0.05) than those in the control group.

CONCLUSIONS: Downregulated expression of Mfn2 may affect the regular development of follicle through the mediation of mTOR signal pathway.

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