The ER is a dynamic structure, capable of changing its cellular organization and distribution patterns remarkably as shown at fertilization of starfish and sea urchin eggs. Here using time-lapse live imaging confocal microscopy, we showed that mouse oocytes undergo a dramatic reorganization of ER during meiotic maturation in vitro and in vivo. GV-stage oocytes contained a fine ER network throughout the interior cytoplasm and cortex. Following GVBD, ER surrounded the spindle during its migration to the oocyte cortex. MII oocytes contained striking ER accumulations at the cortex, with no apparent polarity in relation to the meiotic spindle, similar to those described previously [19, 24, 25]. On the other hand, we first revealed that maternal diabetes is associated with inadequate translocation of ER during oocyte maturation and a high proportion of oocytes from diabetic mice showed morphological abnormalities. Morphological parameters have been widely recognized as an indicator of oocyte quality. In our study, we showed that oocytes with morphological abnormalities degenerated at a high frequency, and only those oocytes with a normal appearance were selected for further analysis. We clearly observed a homogeneous distribution of ER throughout the entire ooplasm during the meiotic maturation process in oocytes from diabetic mice. ER distribution is an indicator for cytoplasmic maturation . Studies have shown that spatial remodeling of endoplasmic reticulum render the oocyte capable of supporting development . The ER is a vast membranous network responsible for protein synthesis and assembly, maturation, and along with the Golgi apparatus, transportation and release of correctly folded proteins. It is also a critical site for Ca2+ homeostasis [10, 27]. Ca2+-ATPases, Ca2+ storage proteins, and specific Ca2+ release channels have been localized to the ER, which permits this organelle to perform a crucial role in the regulation of intracellular Ca2+[28, 29]. Moreover, the ER contains InsP3 receptors and, in some cases, ryanodine receptors, both of which mediate Ca2+ release from the ER . A specialized ER organization in MII mouse oocytes are the cortical ER clusters which act as pacemaker sites for the generation of Ca2+ oscillations at fertilization [31, 32]. The vegetal cortex is more sensitive to InsP3 and Ca2+-releasing sperm extracts  and acts as the Ca2+ wave pacemaker at fertilization [22, 31] and even after fertilization near the spindle . The localization of InsP3Rs to the ER clusters suggests an important role in regulating the initiation of Ca2+ release [20, 33]. Clustering of InsP3Rs in ER increases the sensitivity of Ca2+ release such that coherent signals can be generated in response to very low levels of stimuli that otherwise would not elicit a response . This may be particularly pertinent to fertilization of mammalian eggs where low InsP3 concentrations have been proposed  and where the signaling pathway involves the introduction of a phospholipase C from a very small cell (the sperm) into a very large cell (the egg) . These observations demonstrate that the cortical ER clusters play an important role in the initiation and spatial organization of Ca2+ signaling at fertilization. Thus, we can conclude that inadequate redistribution of ER may be one of the important factors contributing to the maturation delay and spindle/chromosome disorganization observed in diabetic oocytes. However, previous studies revealed that ovulated oocytes from diabetic mice displayed an alteration in mitochondrial ultrastructure, and quantitative analysis of mitochondrial DNA copy number demonstrated an increase . Therefore, the defects in diabetic oocytes might be the interaction between the ER and mitochondria. Taken together, the above results suggest that maternal diabetes leads to inadequate redistribution of ER during oocyte maturation in vitro and in vivo.
As a central regulator of protein quality control, folding, trafficking, and targeting, the ability of the ER to adapt its capacity to manage synthetic, metabolic, and other adverse conditions is of paramount importance for the cell . In the present study we found spindle-associated ER as well as larger areas of ER-fluorescence deeper within the cytoplasm in mouse early embryos. ER displayed a homogeneous distribution pattern throughout the entire ooplasm during development of embryos from diabetic mice. We conclude that the impaired organization of the ER could account for the reduced developmental potential observed in early embryos from diabetic mice.
In addition, very large ER aggregations were seen in GV oocytes or in two-cell embryos from diabetic mice. First, we found that GV oocytes from diabetic mice displayed a significantly higher percentage of aggregated ER distribution areas near the nucleus when compared with controls. These oocytes were not able to resume meiotic maturation and completely deteriorated within a short time. Second, we found that two-cell embryos from diabetic mice showed a higher percentage of very large aggregated ER throughout the cytoplasm when compared to controls. Importantly, most of them were unable to develop further. The ER elicits an elaborate adaptive response known as the unfolded protein response (UPR). Much of the systemic physiology related to its dysfunctions has been viewed in the context of its luminal adaptation to protein processing and folding. In eukaryotic cells, monitoring of the ER lumen and the canonical branches of the UPR are mediated by three ER membrane-associated proteins. In a well-functioning and “stress-free” ER, these transmembrane proteins are bound by a chaperone in their intraluminal domains and rendered inactive [36, 37]. There are three mechanisms to mitigate ER stress which includes reducing protein synthesis, facilitating protein degradation, and increasing production of chaperones that help proteins in the ER lumen to fold. These mechanisms are implicated in resolving stress; if they fail the cell becomes functionally compromised and may undergo apoptosis. Together with our findings, we propose that the very large aggregated ER in oocytes or early embryos may contribute to ER stress and UPR, and hence commit to cell death which needs further detailed investigation.