Increased H3K27ac level of ACE mediates the intergenerational effect of low peak bone mass induced by prenatal dexamethasone exposure in male offspring rats

Cell Death & Disease
Hao XiaoHui Wang

Abstract

Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multiple organs in offspring. Here, we verified the intergenerational effect of low peak bone mass induced by PDE and investigated its intrauterine programming mechanism. Pregnant rats were injected subcutaneously with 0.2 mg/kg/d dexamethasone from gestation day (GD) 9 to 20. Some pregnant rats were killed for the fetuses on GD20, and the rest went on to spontaneous labor to produce the first-generation (F1) offspring. The adult F1 male offspring were mated with normal females to produce the F2 offspring. In vivo, PDE leads to low peak bone mass in F1 male offspring rats at postnatal week (PW) 28. Furthermore, PDE reduced the bone mass in F1 male offspring from GD20 to PW12. Meanwhile, the osteogenic differentiation was suppressed and the local renin-angiotensin system (RAS) was activated continuously by PDE. Moreover, the histone 3 lysine 27 acetylation (H3K27ac) level in angiotensin-converting enzyme (ACE) promoter region was increased by PDE from GD20 to PW12. Likewise, PDE induced the low peak bone mass and the activated local RAS in F2 male offspring. Meaningfully, the H3K27ac level of ACE was increased by PDE in the F2 offspring. In vitro, dexameth...Continue Reading

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Citations

Sep 14, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Songqiang HuangDan Xu
Aug 9, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yinxian WenLiaobin Chen
Aug 28, 2021·International Journal of Molecular Sciences·Huixia YangViktoria von Schönfeldt
Jul 4, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Yi-Zhong WangHui Wang

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
electrophoresis
immunoprecipitation
ChIP
histone acetylation

Software Mentioned

Image
SPSS
GraphPad
Pro Plus
Prism

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