Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats

Abstract

BackgroundMetformin decreases polycystic ovary syndrome (PCOS) symptoms, induces ovulation, and may improve developmental competence of in vitro oocyte maturation. This study was designed to define the effects of metformin on the characteristics of in vitro oocyte maturation in estradiol valerate (EV) PCOS-induced rats.MethodsForty-five adult female Sprague–Dawley rats were randomly divided into control; sham and PCOS-induced (treated by a single dose of estradiol valerate, 4 mg/rat, IM) groups. The body weight was measured weekly for 12 weeks. At the end of week 12, the serum levels of testosterone, estrogen, progesterone, LH, and FSH and blood glucose of all the rats were measured. About 380 cumulus oocyte complexes (control, 125; sham, 122; PCOS-induced rats, 133) were incubated in Ham’s F10 in the absence and/or presence of metformin (M 5−10) for 12, 24, 36, and 48 h. The cumulus cells expansion and nuclear and cytoplasmic maturation of the oocytes was evaluated using 1 % aceto-orcein staining, and transmission electron microscopy (TEM).ResultsNo significant differences were observed in the body weight of the rats. The serum level of testosterone was reduced, and progesterone and LH were significantly increased in the PCOS-induced rats (p < 0.05). However, no significant differences were observed in the serum levels of estrogen and FSH among the groups. Blood glucose level was higher in the PCOS-induced rats than control, (p < 0.01). The expansion of cumulus cells was observed in the metformin-treated oocytes. The oocytes retrieved from PCOS-induced rats show a stage of meiotic division (GVBD, MI, A-T, and MII) in 57.12 % of metformin-untreated and fairly significantly increased to 64.28 % in metformin-treated oocytes, (p < 0.05), but no differences were observed in the MII stage within groups. The redistribution of some cytoplasmic organelles throughout the ooplasm, particularly the peripheral cortical granules, was defined in the metformin-treated oocytes.ConclusionsSingle dose of EV can creates a reversible PCO adult rat model. Metformin enhances the COCs to initiate meiotic resumption at the first 6 h of IVM. In our study the metformin inability to show all aspects of in vitro oocyte maturation and may be resulted from deficiency of EV to induce PCOS.

Animal models of polycystic ovary syndrome: A review of hormone‐induced rodent models focused on hypothalamus‐pituitary‐ovary axis and neuropeptides

“…EV is a long‐acting estrogen. Rat models of EV‐induced PCOS have been established by injecting young adult female rats in estrus with a single dose of 2‐4 mg EV …”

Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model

“…In rats, metformin improves ovarian function in animals with permanent androgen-induced estrus [ 13 – 15 ]. In our previous studies, the percentage of neonatally androgenized rats with PCOS was approximately 50 and 10% become pregnant after metformin treatment.…”

Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway

“…The PCOS rat model was induced by a single dose of estradiol valerate (EV; 4 mg/rat, intramuscular) as described previously (31). The rats were divided into eight groups (n=12 per group) as follows: Control group (Control Veh), normal rats treated with 500 mg/kg/day metformin orally (Control Met), normal rats treated with 20 mg/kg/day pioglitazone orally (Control Pio), normal rats treated with 500 mg/kg/day metformin plus 20 mg/kg/day pioglitazone orally (Control Met + Pio), PCOS group (PCOS Veh), PCOS rats treated with 500 mg/kg/day metformin orally (PCOS Met), PCOS rats treated with 20 mg/kg/day pioglitazone orally (PCOS Pio) and PCOS rats treated with 500 mg/kg/day metformin plus 20 mg/kg/day pioglitazone orally (PCOS Met + Pio).…”