title: Does metformin improve in vitro maturation and ultrastructure of oocytes retrieved from estradiol valerate polycystic ovary syndrome-induced rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Forty-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).
  
  
  RESULTS
  No 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.
  
  
  CONCLUSIONS
  Single 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.
authors.affiliation: Department of Anatomical Sciences, Shiraz University of Medical Sciences, Shiraz, 71348-53185, Iran. mesbahf@sums.ac.ir.|Embryonic Stem Cell Lab, Shiraz University of Medical Sciences, Shiraz, Iran. mesbahf@sums.ac.ir.
authors.forename: Fakhroddin
authors.initials: F
authors.lastname: Mesbah
authors.affiliation: Department of Anatomical Sciences, Shiraz University of Medical Sciences, Shiraz, 71348-53185, Iran. Mohsen.moslem@gmail.com.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Moslem
authors.affiliation: Department of Anatomical Sciences, Shiraz University of Medical Sciences, Shiraz, 71348-53185, Iran. vojdaniz@sums.ac.ir.|Embryonic Stem Cell Lab, Shiraz University of Medical Sciences, Shiraz, Iran. vojdaniz@sums.ac.ir.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Vojdani
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. mirkhanh@sums.ac.ir.|Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. mirkhanh@sums.ac.ir.
authors.forename: Hossein
authors.initials: H
authors.lastname: Mirkhani
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003270:Contraceptive Agents / Q000633:toxicity*; D054885:Cumulus Cells / Q000187:drug effects; D004195:Disease Models, Animal; D004958:Estradiol / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D005300:Fertility Agents, Female / Q000494:pharmacology*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D066298:In Vitro Techniques; D008687:Metformin / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D009865:Oocytes / Q000187:drug effects* / Q000648:ultrastructure; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D003270:Contraceptive Agents; D005300:Fertility Agents, Female; D012739:Gonadal Steroid Hormones; D004958:Estradiol; D008687:Metformin