EFFECTS OF THE COMBINATION OF OESTRADIOL VALERATE AND MEDROXYPROGESTERONE ACETATE IN REPAIRING PREMATURE OVARIAN FAILURE BY REGULATING PI3K/AKT/MTOR SIGNALLING PATHWAY-RELATED PROTEINS

Huiling Bi, Congxiu Miao^*

Department of Reproduction and Genetics, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi Province, China

Objective: To analyse the effects of the combination of oestradiol valerate (EV) and medroxyprogesterone acetate (DMPA) on premature ovarian failure (POF) by regulating the phosphatidylinositol-3-hydroxykinase/protein kinase B/mammalian rapamycin target protein (PI3K/AKT/mTOR) signalling pathway. 

Methods: Sixty healthy adult female SD mice were divided into three groups: the control group; the model group; and the EV+DMPA group. Triptolide (TP) was given to both the model group and the EV+DMPA group. After modelling, the EV+DMPA group was given the EV and DMPA solution by gavage. Blood was taken from the abdominal aorta under anaesthesia. Serum oestradiol (E2), progesterone (P), and anti-Müllerian tube stimulation were detected using an enzyme-linked immunosorbent assay. The levels of anti-Müllerian hormone (AMH), follicle stimulating hormone (FSH), luteinising hormone (LH), endothelin (ET), and nitric oxide (NO) were calculated. Haematoxylin-eosin (HE) staining was used to observe the histopathological changes of the ovaries. The number of secondary follicles, sinus follicles, corpus luteums, and atretic follicles were calculated. A Western blot analysis was used to detect the relative expression or phosphorylation levels of p-PI3K, p-mTOR, and p-AKT. 

Results: In the model group, the levels of E2, P, and AMH were significantly lower than those in the control group, and the levels of FSH and LH were significantly higher than those in the control group. In the EV+DMPA group, the levels of E2, P, and AMH were significantly higher than those in the model group, and the levels of FSH and LH were significantly lower than those in the model group (P<0.05). In the model group, the levels of ET and ET/NO were significantly higher than those in the control group, and the level of NO in the control group was significantly higher than that in the control group. In the EV+DMPA group, the levels of ET and ET/NO were significantly lower than those in the model group, and the level of NO was significantly higher than that in the model group (P<0.05). In the control group, the medullary structure was clear, both the morphology and number of ovaries at all levels were normal, and there were more corpus luteums and an abundance of blood vessels. The volume of ovaries in the model group was significantly reduced and there were fewer mature ovaries. In the EV+DMPA group, the volume of ovaries was higher than that in the model group, and there were more mature follicles and corpus luteums than in the model group. The number of secondary follicles, sinus follicles, and corpus luteums in the model group were significantly lower than those in the control group, and the number of atretic follicles was significantly higher than that in the control group. The number of secondary follicles, sinus follicles, and corpus luteums in the EV+DMPA group were significantly higher than those in the model group, and the number of atretic follicles was significantly lower than that in the model group (P<0.05). In the model group, the p-PI3K, p-AKT, and p-mTOR levels were significantly lower than those in the control group, while the p-PI3K, p-AKT, and p-mTOR levels in the EV+DMPA group were significantly higher than those in the model group (P<0.05). 

Conclusion: The combination of EV and DMPA can improve sex hormone levels, restore the number of follicles and corpus luteums in mice with POF, and repair ovarian damage caused by TP, the mechanism of which may be related to the regulation of the PI3K/AKT/mTOR signalling pathway-related proteins using EV and DMPA.