Abstract
BackgroundMaternal 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.MethodsWe 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.ResultsWe 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.ConclusionsWe suggest that the effects of maternal diabetes on imprinted genes may primarily be caused by the adverse uterus environment.
Highlights
Maternal diabetes mellitus has severe deleterious effects on fetal development, and it affects transmission to the generation
We have found that the DNA methylation patterns in Differentially Methylated Regions (DMRs) of imprinted genes Peg3, Snrpn and H19 in oocytes was not altered by maternal diabetes at 15 days of injection of STZ [23], but the embryonic development was affected
We found that the expression and methylation levels of the imprinted genes were altered by maternal diabetes mellitus in placentas at 10.5dpc of gestation
Summary
Maternal diabetes mellitus has severe deleterious effects on fetal development, and it affects transmission to the generation. The effects of maternal diabetes mellitus on fetal development have been studied in various animal models. Moley et al showed that the mRNA and protein expression of the glucose transporters GLUT-1, GLUT-2, and GLUT-3 were decreased in embryos from streptozotocin (STZ)induced hyperglycaemic mice [12]. These results partly elucidate how maternal diabetes mellitus causes abnormal embryo development. It is still not clear how the adverse effects are inherited to the generations
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have