Disordered Meiotic Regulation of Oocytes by Duration of Diabetes Mellitus in BBdp Rat

Abstract

Diabetes mellitus (DM) disturbs normal functions from the level of cells to the level of organs. In this study, the authors explore the detrimental effects of type 1 diabetes on meiotic regulation depending on the duration of DM. In non-diabetes-prone BioBreeding (BBdr) control rats, most of the large follicles had germinal vesicle (GV)-intact oocytes. Conversely, a decrease of intact GV that was dependent on the duration of diabetic symptoms was observed; only 54% of the large follicles of diabetes-prone BB (BBdp) rats had GV-intact oocytes at 6 weeks after diabetes induction. Furthermore, some of the secondary follicles in BBdp rats also had germinal vesicle breakdown (GVB) oocytes. The nuclear status of the euglycemia BBdp rat was similar to those of the BBdr rat. In BBdp rats, the rate of meiotic progression to the metaphase II stage was significantly lower; however, the rate of segregated oocytes was significantly increased compared with controls during induction of in vitro maturation. The rate of segregated oocytes was not affected by the presence of the cumulus after chronic symptoms. These results indicate that chronic DM has a detrimental effect on meiotic regulation during folliculogenesis and results in a reduced number of competent oocytes. In addition, these data suggest that the follicle cells can resume supporting the meiotic regulation under euglycemia through insulin administration, independent of the duration of DM.

Islet transplantation reverses the effects of maternal diabetes on mouse oocytes

“…Our results showed that insulin treatment could partly cure but not completely reverse the effects of diabetes on oocytes, which were contradictory to earlier studies (Colton et al 2002, Kim et al 2007). We speculate that there were two reasons for this contradiction.…”

“…The delay in oocyte meiotic maturation was improved with insulin treatment during superovulation (Colton et al 2002). Kim et al (2007) also observed that insulin reverses the diabetes effect on in vitro maturation effects of the chronic diabetes-prone BioBreeding rats. However, we found that the ovulation rate of mice with severe hypoglycemia was lower than that of controls after insulin treatment.…”

“…Even though improvements in glycemic control throughout pregnancy have drastically reduced the incidence of spontaneous abortions and congenital malformations in infants delivered by women with diabetes, the incidence of the aforementioned pregnancy complications has increased by three-to fivefold (El-Sayed & Lyell 2001, Baccetti et al 2002. The ability of insulin to curtail delays in oocyte meiotic maturation caused by type 1 diabetic insults has been confirmed in studies from several different laboratories (Colton et al 2002, Kim et al 2007. Rates of GVBD and ovulation were significantly lower in streptozotocin (STZ)-treated mice than those in control mice.…”

“…Emerging evidence has implicated that these effects are associated with compromised oocyte maturation (Colton et al 2002, Doblado & Moley 2007. A decrease in the rate of germinal vesicle breakdown (GVBD; Diamond et al 1989, Colton et al 2002, Chang et al 2005, Kim et al 2007, Ratchford et al 2007) and the number of ova at metaphase II (MII; Colton et al 2002), both of which are markers of oocyte nuclear maturation, were observed in superovulated oocytes obtained from diabetic mice; furthermore, mitochondrial dysfunction, spindle disorganization, chromosome misalignment, and aneuploidy were observed (Goud et al 2006, Wang et al 2009), indicating the abnormal cytoplasmic maturation of superovulated oocytes obtained from diabetic mice. Since maternal diabetes compromises oocyte maturation and affects the subsequent embryo development, it is necessary to explore the effective ways to reduce damage to oocytes caused by diabetes.…”

The pivotal role of glucose metabolism in determining oocyte developmental competence

“…In addition, mouse oocytes from pre-ovulatory follicles are w30% smaller in size compared to oocytes from control animals (Chang et al 2005). Secondly, COCs from chemically induced diabetic mice exhibit aberrant nuclear maturation, with precocious resumption of meiosis during spontaneous maturation and decreased efficiency of induced maturation, leading to an MI-MII transition block in both models (Kim et al 2007). Poor nuclear maturation was attributed to decreased de novo purine and cAMP synthesis as a result of decreased flux of glucose through PPP (Colton et al 2003).…”