title: Retardation of fetal dendritic development induced by gestational hyperglycemia is associated with brain insulin/IGF-I signals.
abstract: Hyperglycemia is an essential risk factor for mothers and fetuses in gestational diabetes. Clinical observation has indicated that the offspring of mothers with diabetes shows impaired somatosensory function and IQ. However, only a few studies have explored the effects of hyperglycemia on fetal brain development. Neurodevelopment is susceptible to environmental conditions. Thus, this study aims to investigate the effects of maternal hyperglycemia on fetal brain development and to evaluate insulin and insulin-like growth factor-I (IGF-I) signals in fetal brain under hyperglycemia or controlled hyperglycemia. At day 1 of pregnancy, gestational rats were intraperitoneally injected with streptozocin (60 mg/kg). Some of the hyperglycemic gestational rats were injected with insulin (20 IU, two times a day) to control hyperglycemia; the others were injected with saline of equal volume. The gestational rats were sacrificed at days 14, 16, and 18 of embryo development. The dendritic spines of subplate cortex neurons in the fetal brain were detected by Golgi-Cox staining. The mRNA levels of insulin receptors (IRs) and IGF-IR in the fetal brain were measured using qRT-PCR. The protein levels of synaptophysin, IR, and IGF-IR in the fetal brain were detected by western blot. No significant difference in fetal brain formation was observed between the maternal hyperglycemic group and insulin-treated group. By contrast, obvious retardation of dendritic development in the fetus was observed in the maternal hyperglycemic group. Similarly, synaptophysin expression was lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. The mRNA and protein expression levels of IRs in the fetal brain were higher in the hyperglycemic group than in the insulin-treated group. By contrast, the levels of IGF-IR in the brain were lower in the fetus of the maternal hyperglycemic group than in that of the insulin-treated group. These results suggested that maternal hyperglycemia can retard dendritic development in the fetal brain and that these changes partially resulted from abnormal insulin/IGF-I signaling in the fetal brain.
authors: Institute of Anatomy and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Lanzhou University, Lanzhou, PR China. Electronic address: jingyh@lzu.edu.cn.
authors: Yu-Hong
authors: YH
authors: Jing
authors: Institute of Anatomy and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors: Yan-Feng
authors: YF
authors: Song
authors: Institute of Anatomy and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors: Ya-Ming
authors: YM
authors: Yao
authors: Institute of Anatomy and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors: Jie
authors: J
authors: Yin
authors: Institute of Anatomy and Embryology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors: De-Gui
authors: DG
authors: Wang
authors: Institute of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, PR China.
authors: Li-Ping
authors: LP
authors: Gao
mesh_terms: D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000473:pathology*; D003712:Dendrites / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005333:Fetus; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy; D007328:Insulin / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D009474:Neurons / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016622:Silver Staining; D018709:Statistics, Nonparametric; D013311:Streptozocin / Q000633:toxicity; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D013311:Streptozocin; D007334:Insulin-Like Growth Factor I
keywords: Dendritic spine; Fetal brain development; Gestational hyperglycemia; Insulin/IGF-I