title: Diabetic uterus environment may play a key role in alterations of DNA methylation of several imprinted genes at mid-gestation in mice.
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.
authors.forename: Zhao-Jia
authors.initials: ZJ
authors.lastname: Ge
authors.forename: Qiu-Xia
authors.initials: QX
authors.lastname: Liang
authors.forename: Shi-Ming
authors.initials: SM
authors.lastname: Luo
authors.forename: Yan-Chang
authors.initials: YC
authors.lastname: Wei
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Han
authors.forename: Heide
authors.initials: H
authors.lastname: Schatten
authors.affiliation: Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, P, R, China. sunqy@ioz.ac.cn.
authors.forename: Qing-Yuan
authors.initials: QY
authors.lastname: Sun
authors.forename: Cui-Lian
authors.initials: CL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D018392:Genomic Imprinting; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000378:metabolism*; D055517:snRNP Core Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C094335:H19 long non-coding RNA; D051741:Kruppel-Like Transcription Factors; C097901:Peg3 protein, mouse; D062085:RNA, Long Noncoding; D055517:snRNP Core Proteins