Accordingly, our findings suggest that excess ROS generated by neurons following high glucose exposure directly inhibited the neurons’ development. The idea that excess ROS affects NCCs development in diabetic pregnancies is supported in the literatures. This suggests that the malformations which developed in the neural tube, dorsal root ganglia and nerves in the limb buds were the results of impaired NCCs development caused by excess ROS in presence of high glucose. It has been reported that vitamin C supplements added to the diet of pregnant diabetic rats could reduced the rate of embryo malformations and fetal resorption. In another word, vitamin C could act as an antioxidant to neutralize excess ROS produced in embryonic tissues. Our study supports this idea because we demonstrated that adding vitamin C to our cultured neurons could inhibit the damaging effects of high glucose on the neurons. Moreover, since we showed that vitamin C decreases ROS generation, it implies that vitamin C exerted its effect by inhibiting ROS rather than directly protecting the cells. Undifferentiated somatic cells surrounding the egg nests differentiate into pregranulosa cells, and invade the egg nest to encircle individual oocytes forming primordial follicles. Pregranulosa cells become granulosa cells once primordial follicles are formed, and this represents the first critical morphogenetic process in folliculogenesis. Defect in primordial follicle formation may lead to premature ovarian failure and infertility. The regulation of primordial follicle morphogenesis is not well understood. Deletion of GDF9 or BMP15, or inactivation of endogenous FSH adversely affects primordial follicle formation. Estradiol-17?, at physiological dose level, supports follicle formation. E as well as ESR1 and ESR2 levels increase during primordial follicle formation in vivo. E promotes primordial follicle formation in vivo and in vitro. However the mediators of E action are yet to be identified. Proteomic analysis of developing hamster ovaries has identified ERBB3 binding protein 1 to be significantly downAbMole 28-demethyl-beta-amyrone regulated in hamster ovaries on postnatal day 8 when morphologically distinct primordial follicles can be first identified. EBP1, the human homolog of PA2G4 family of proteins, is transcribed from the gene PA2G4. EBP1 has a 48 kDa and a 42 kDa isoforms; however, the 48 kDa isoform predominates in mammals, including the hamster. EBP1 is highly conserved in eukaryotes, ubiquitously expressed in tissues and structurally similar to methionine aminopeptidase. It plays an important role in cell proliferation and differentiation. Binding of EBP1 to the 15 amino acid juxtamembrane domain of ERBB3 via its 1�C105 amino acid region at the N-terminal end is regulated by PKC. Heregulin phosphorylates EBP1 at ser360 causing it to dissociate from ERBB3. Phosphorylated EBP1 associates with phosphorylated AKT as well as migrates to the nucleus. Overexpression of EBP1 leads to cell cycle arrest in breast cancer cells and fibroblasts.