TY  - JOUR
A1  - Dwi Putra, Sulistyo Emantoko
A1  - Reichetzeder, Christoph
A1  - Hasan, Ahmed Abdallah Abdalrahman Mohamed
A1  - Slowinski, Torsten
A1  - Chu, Chang
A1  - Krämer, Bernhard K.
A1  - Kleuser, Burkhard
A1  - Hocher, Berthold
T1  - Being born large for gestational age is associated with increased global placental DNA methylation
JF  - Scientific Reports
N2  - Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p<0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p<0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p=0.001).
KW  - fetal origins hypothesis
KW  - birth weight
KW  - repetitive elements
KW  - glucocorticoid receptor
KW  - nutrient transport
KW  - growth restriction
KW  - later health
KW  - pregnancy
KW  - genes
KW  - patterns
Y1  - 2020
U6  - https://doi.org/10.1038/s41598-020-57725-0
SN  - 2045-2322
VL  - 10
IS  - 1
SP  - 1
EP  - 10
PB  - Springer Nature
CY  - London
ER  - 
TY  - JOUR
A1  - Putra, Sulistyo Emantoko Dwi
A1  - Neuber, Corinna
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
A1  - Kleuser, Burkhard
T1  - Analysis of genomic DNA methylation levels in human placenta using liquid Chromatography-Electrospray ionization tandem mass spectrometry
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background: DNA-methylation is a common epigenetic tool which plays a crucial role in gene regulation and is essential for cell differentiation and embryonic development. The placenta is an important organ where gene activity can be regulated by epigenetic DNA modifications, including DNA methylation. This is of interest as, the placenta is the interface between the fetus and its environment, the mother. Exposure to environmental toxins and nutrition during pregnancy may alter DNA methylation of the placenta and subsequently placental function and as a result the phenotype of the offspring. The aim of this study was to develop a reliable method to quantify DNA methylation in large clinical studies. This will be a tool to analyze the degree of DNA methylation in the human placenta in relationship to clinical readouts. Methods: Liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MS) technique was used for the quantification of the 5dmC/dG ratio in placentas from 248 healthy pregnancies. We were able to demonstrate that this method is a reliable and stable way to determine global placental DNA methylation in large clinical trials. Results/Conclusion: The degree of placental DNA methylation seen in our pilot study varies substantially from 2% to 5%. The clinical implications of this variation need to be demonstrated in adequately powered large studies.
KW  - Pregnancy
KW  - Placenta
KW  - Methylation
KW  - Global
KW  - LC-MS/MS
KW  - Fetal programming
KW  - Clinical
Y1  - 2014
U6  - https://doi.org/10.1159/000358666
SN  - 1015-8987
SN  - 1421-9778
VL  - 33
IS  - 4
SP  - 945
EP  - 952
PB  - Karger
CY  - Basel
ER  -