Diabetic uterus environment may play a key role in alterations of DNA methylation of several imprinted genes at mid-gest
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RESEARCH
Open Access
Diabetic uterus environment may play a key role in alterations of DNA methylation of several imprinted genes at mid-gestation in mice Zhao-Jia Ge1,2,3, Qiu-Xia Liang3, Shi-Ming Luo3, Yan-Chang Wei3, Zhi-Ming Han3, Heide Schatten4, Qing-Yuan Sun3* and Cui-Lian Zhang1*
Abstract Background: Maternal diabetes mellitus not only has severe deleterious effects on fetal development, but also it affects transmission to the next generation. However, the underlying mechanisms for these effects are still not clear. Methods: We investigated the methylation patterns and expressions of the imprinted genes Peg3, Snrpn, and H19 in mid-gestational placental tissues and on the whole fetus utilizing the streptozotocin (STZ)-induced hyperglycemic mouse model for quantitative analysis of methylation by PCR and quantitative real-time PCR. The protein expression of Peg3 was evaluated by Western blot. Results: We found that the expression of H19 was significantly increased, while the expression of Peg3 was significantly decreased in dpc10.5 placentas of diabetic mice. We further found that the methylation level of Peg3 was increased and that of H19 was reduced in dpc10.5 placentas of diabetic mice. When pronuclear embryos of normal females were transferred to normal/diabetic (NN/ND) pseudopregnant females, the methylation and expression of Peg3 in placentas was also clearly altered in the ND group compared to the NN group. However, when the pronuclear embryos of diabetic female were transferred to normal pesudopregnant female mice (DN), the methylation and expression of Peg3 and H19 in dpc10.5 placentas was similar between the two groups. Conclusions: We suggest that the effects of maternal diabetes on imprinted genes may primarily be caused by the adverse uterus environment. Keywords: Maternal diabetes milieu, DNA imprinting, Placenta
Background Infants of mothers with pre-existing types 1, 2 or gestational diabetes have significantly higher rates of perinatal mortality and major congenital anomaly [1,2]. Diabetic embryopathy can affect many organ systems including the heart and the neural tube [3-5]. The effects of maternal diabetes mellitus on fetal development have been studied in various animal models. In drug-induced animal models, embryo development was disturbed by maternal hyperglycaemia [6,7]. In non-obese diabetic (NOD) mouse models * Correspondence: [email protected]; [email protected] 3 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China 1 Reproductive Medicine Center, Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, P. R. China Full list of author information is available at the end of the article
of spontaneous type 1 diabetes mellitus, only 20% of recovered NOD embryos reached the blastocyst stage at 96 hours of superovulation compared with 90% of embryos recovered from nondiabetic animals [6]. Several reports have shown that teratogenesis may be a direct result of hyperglycemia [8,9]. Previous studies found t
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