Prenatal nicotine exposure intergenerationally programs imperfect articular cartilage via histone deacetylation through maternal lineage.
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2018
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Abstract
Accumulating evidence has shown that the impact of prenatal environmental factors on the organs of the offspring could last until the adulthood. Here, we aimed to investigate these effects and the potential mechanism of prenatal nicotine exposure (PNE) on the female adult cartilage of the first generation (PNE-F1) and the second generation (PNE-F2). Pregnant Wistar rats were injected with 2.0 mg/kg.d nicotine from gestational day (GD) 9 to 20. Then their F1 generation at GD20 and postnatal week (PW) 12, and F2 generation at PW12 were harvested. The expression of extracellular matrix (ECM) and transforming growth factor β (TGFβ) signaling genes were analyzed by real-time quantitative PCR, and the histone acetylation was examined by chromatin immunoprecipitation assay. The results showed that PNE reduced the ECM and TGFβ signaling gene expressions in both PNE-F1 and PNE-F2 female adult articular cartilage. In the F1 generation, PNE inhibited the acetylation at H3K9 of TGFβ, TGFβ receptor 1 (TGFβR1), SRY-type high mobility group box 9 (SOX9), a1 chain of type II collagen (COL2A1) and aggrecan (ACAN) gene promoters at both GD20 and PW12. In PNE-F2 at PW12, the obvious deacetylation at H3K9 of the TGFβR1 and COL2A1 promoters still existed. Moreover, in rat fetal chondrocytes, corticosterone rather than nicotine directly induced the hypoacetylation of H3K9 of TGFβR1 and COL2A1 genes, which might be the main cause of imperfect cartilage for PNE-F2. This study may be helpful to elucidate the developmental variability of articular cartilage quality and useful for the early prevention of articular damage.
| Reference Key |
xie2018prenataltoxicology
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| Authors | Xie, Zhe;Zhao, Zhe;Yang, Xu;Pei, Linguo;Luo, Hanwen;Ni, Qubo;Li, Bin;Qi, Yongjian;Tie, Kai;Magdalou, Jacques;Chen, Liaobin;Wang, Hui; |
| Journal | toxicology and applied pharmacology |
| Year | 2018 |
| DOI |
S0041-008X(18)30104-2
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