Prenatal nicotine exposure (PNE) could induce an increased susceptibility to multiple chronic diseases in adult offspring, that mainly caused by intrauterine maternal glucocorticoid (GC) over-exposure. We investigated the changes and inheritability of hepatic glucose and lipid metabolism caused by PNE, to decipher the possible intrauterine programming mechanism. Pregnant Wistar rats were administered subcutaneously with 2 mg/kg·d nicotine from gestational day (GD) 9∼20, and second-generation (F2) were set according to the mating between control females and PNE males. The results showed that serum phenotypes and hepatic enzymes of glucose and lipid metabolism were lower in F1 fetal rats of PNE but higher in the F1 adult rats. Meanwhile, the activated states of hepatic glucocorticoid-activation system, including type 1 and type 2 11β-hydroxysteroid dehydrogenases (Hsd11b1/2), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and CCAAT enhancer binding protein α (Cebpa), were positively correlated with serum corticosterone levels but negatively correlated with the histone acetylation (H3K27ac) and expression levels of insulin-like growth factor 1 (Igf1) before and after birth. Furthermore, serum phenotypes and hepatic enzymes of glucose and lipid metabolism were lower in both F2 fetal and adult rats of PNE, which were consistent with the hepatic changes of GC-IGF1 axis and the glucocorticoid-activation system. In conclusion, PNE could lead to inheritable changes of hepatic glucose and lipid metabolism, which are related to the intrauterine programming of GC-IGF1 axis induced by the glucocorticoid-activation system.

中文翻译：

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产前尼古丁暴露对后代大鼠肝葡萄糖和脂质代谢的影响及其遗传性。

产前尼古丁暴露（PNE）可能导致成年后代对多种慢性疾病的敏感性增加，这主要是由宫内孕产妇糖皮质激素（GC）过度暴露引起的。我们调查了由PNE引起的肝糖脂代谢的变化和遗传性，以探讨可能的子宫内编程机制。从妊娠第9天到第20天，给Wistar大鼠皮下注射2 mg / kg·d的尼古丁，并根据雌性和雄性PNE之间的交配设定第二代（F2）。结果表明，F1胎鼠PNE的血清表型和肝酶的葡萄糖和脂质代谢水平较低，而F1成年鼠的血清表型和肝酶水平较高。同时，肝糖皮质激素激活系统的激活状态，包括1型和2型11β-羟类固醇脱氢酶（Hsd11b1 / 2），核受体亚家族3，C组，成员1（Nr3c1）和CCAAT增强子结合蛋白α（Cebpa）与血清皮质酮水平呈正相关，但与出生前后的组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1（Igf1）的表达水平。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝糖和脂质代谢的遗传性变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。C组核受体亚家族3（成员1（Nr3c1）和CCAAT增强子结合蛋白α（Cebpa））与血清皮质酮水平呈正相关，而与组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1表达水平呈负相关（IGF1）出生前后。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。C组核受体亚家族3（成员1（Nr3c1）和CCAAT增强子结合蛋白α（Cebpa））与血清皮质酮水平呈正相关，而与组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1表达水平呈负相关（IGF1）出生前后。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。成员1（Nr3c1）和CCAAT增强子结合蛋白α（Cebpa）与出生前和出生后血清皮质酮水平呈正相关，而与组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1（Igf1）的表达水平呈负相关。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。成员1（Nr3c1）和CCAAT增强子结合蛋白α（Cebpa）与出生前和出生后血清皮质酮水平呈正相关，而与组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1（Igf1）的表达水平呈负相关。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。与出生前和出生后血清皮质酮水平呈正相关，而与组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1（Igf1）的表达水平呈负相关。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。与出生前和出生后血清皮质酮水平呈正相关，而与组蛋白乙酰化（H3K27ac）和胰岛素样生长因子1（Igf1）的表达水平呈负相关。此外，F2胎儿和成年PNE大鼠的血清表型，葡萄糖和脂质代谢的肝酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。F2胎儿和成年PNE大鼠的血清表型和肝糖，糖代谢的酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。F2胎儿和成年PNE大鼠的血清表型和肝糖，糖代谢的酶均较低，这与GC-IGF1轴和糖皮质激素激活系统的肝变化一致。总之，PNE可能导致肝脏葡萄糖和脂质代谢的遗传变化，这与糖皮质激素激活系统诱导的宫内编程GC-IGF1轴有关。