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.
Highlights
Metformin decreases polycystic ovary syndrome (PCOS) symptoms, induces ovulation, and may improve developmental competence of in vitro oocyte maturation
Measurement of weight, sex hormones and blood glucose The gain in body weight of the rats within the groups showed a growing trend, the mean (±SD) of the body weight of the rats from week 1 to week 12 increased from 186.20 ± 6.40 to 205.06 ± 3.50 g in the control group, from 186.60 ± 4.53 to 205.60 ± 2.10 g in the sham group, and from 170.26 ± 5.67 to 192.13 ± 2.10 g in the PCOSinduced group, no significant differences were observed in the body weight of the rats
Our findings concur with those of previous studies and show that in the presence of metformin in PCOS-induced rats, a higher number of cumulus cells of cumulus oocyte complexes (COCs) (53.03 %) are completely expanded as compared to those in the absence of metformin (32.83 %). This contradicts the findings of Tosca et al who concluded that metformin inhibits cumuli expansion and oocyte meiotic resumption in bovine COCs, [45]. These results indicate that the presence of metformin in the culture medium may enhance the expansion of cumulus cells, but not in PCOS-induced rats, because metformin acts first on cumulus cell to dissociate around the oocyte [45]
Summary
Metformin 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. Polycystic ovary syndrome is one of the major causes of anovulatory infertility in women. Drug treatments include the administration of metformin, glitazones, spironolactone, estrogen, and clomiphene citrate [5]. Metformin alone or in combination with other drugs is used to treat PCOS. In women with PCOS associated with anovulation and resistance to clomiphene citrate, the administration of clomiphene citrate in combination with metformin satisfactorily increases the ovulation and pregnancy rate [6]
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