Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner.

Abstract:

: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.

journal_name

Epigenetics

journal_title

Epigenetics

authors

Hocher B,Haumann H,Rahnenführer J,Reichetzeder C,Kalk P,Pfab T,Tsuprykov O,Winter S,Hofmann U,Li J,Püschel GP,Lang F,Schuppan D,Schwab M,Schaeffeler E

doi

10.1080/15592294.2016.1184800

subject

Has Abstract

pub_date

2016-07-02 00:00:00

pages

539-52

issue

7

eissn

1559-2294

issn

1559-2308

journal_volume

11

pub_type

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