TY  - JOUR
A1  - Hocher, Berthold
A1  - Haumann, Hannah
A1  - Rahnenführer, Jan
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Pfab, Thiemo
A1  - Tsuprykov, Oleg
A1  - Winter, Stefan
A1  - Hofmann, Ute
A1  - Li, Jian
A1  - Püschel, Gerhard Paul
A1  - Lang, Florian
A1  - Schuppan, Detlef
A1  - Schwab, Matthias
A1  - Schaeffeler, Elke
T1  - Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner
JF  - Epigenetics : the official journal of the DNA Methylation Society
N2  - Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.
KW  - Epigenetics
KW  - eNOS
KW  - Fetal programming
KW  - fatty liver
KW  - metabolism
Y1  - 2016
U6  - https://doi.org/10.1080/15592294.2016.1184800
SN  - 1559-2294
SN  - 1559-2308
VL  - 11
SP  - 539
EP  - 552
PB  - Routledge, Taylor & Francis Group
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Schlemm, Ludwig
A1  - Haumann, Hannah
A1  - Li, Jian
A1  - Rahnenführer, Jan
A1  - Guthmann, Florian
A1  - Bamberg, Christian
A1  - Kalk, Philipp
A1  - Pfab, Thiemo
A1  - Chen, You-Peng
T1  - Offspring sex determines the impact of the maternal ACE I/D polymorphism on maternal glycaemic control during the last weeks of pregnancy
JF  - Journal of the renin angiotensin aldosterone system
N2  - Hypothesis/Introduction: We recently demonstrated that fetal sex may affect maternal glycaemic control in genetically prone mothers. We tested the hypothesis that fetal sex/fetal Y/X chromosomes might affect maternal glycaemic control during pregnancy depending on the maternal angiotensin converting enzyme (ACE) I/D polymorphism.
 Material and methods: One thousand, three hundred and thirty-two Caucasian women without pre-existing diabetes and pre-existing hypertension with singleton pregnancies delivering consecutively at the Charite obstetrics department were genotyped. Glycaemic control was analysed by measuring total glycated haemoglobin at birth. Correction for confounding factors and multiple testing was done.
 Results: Maternal ACE I/D polymorphism showed significant interaction with fetal sex concerning maternal total glycated haemoglobin. Total glycated haemoglobin in DD mothers delivering boys was 6.42 +/- 0.70% vs. 6.21 +/- 0.66% in DD mother delivering girls (p < 0.005), whereas the II carrying mothers showed the opposite effect. II mothers delivering a girl had a higher (p = 0.044) total glycated haemoglobin at birth (6.40 +/- 0.80%) compared to II mothers delivering boys (6.21 +/- 0.81%). There was no interaction of the ACE I/D polymorphism and fetal sex with respect to new onset proteinuria, new onset edema and pregnancy-induced hypertension.
 Conclusions: Maternal glycaemic control during the last weeks of pregnancy seems to be influenced by an interaction of the ACE I/D genotyp and fetal sex.
KW  - ACE I/D polymorphism
KW  - pregnancy
KW  - fetal sex
KW  - pregnancy induced diabetes
KW  - total glycated hemoglobin
KW  - glycemic control during pregnancy
Y1  - 2011
U6  - https://doi.org/10.1177/1470320310387843
SN  - 1470-3203
VL  - 12
IS  - 3
SP  - 254
EP  - 261
PB  - Sage Publ.
CY  - London
ER  -