Objective: To explore the effects of different dosages of 4-nonylphenol (4-NP) on the fatty acid synthesis and estrogen receptor α (ERα) expression in the livers of F1 and F2 rats. Method: Pregnant rats were randomly divided into four groups: control, NP-5 (5 μg per kg per day), NP-25 (25 μg per kg per day) and NP-125 (125 μg per kg per day). 4-NP was gavaged from gestation day (GD) 6 to postnatal day (PND) 21. Some female rats from the experimental groups were mated with male rats from the control group to obtain the F2 rats. F1 generation rats (23 weeks old) and F2 generation rats (13 weeks old) were killed to detect blood biochemistry and the expression of genes and proteins. Results: Compared with the control group, 4-NP (NP-5, NP-25 and NP-125) can increase the liver organ coefficient of the F1 male offspring (P < 0.05 or P < 0.01). The concentration of high density lipoprotein (HDL) in the F1 female NP-5 group was significantly higher than that of the control group (P < 0.01); other indicators had not changed, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and low density lipoprotein (LDL). As the dosage of 4-NP increased, more significant changes of blood biochemistry were found, especially in the NP-125 rats (P < 0.05 or P < 0.01). The changes of histopathology by liver biopsy were consistent with biochemical indices of blood (P < 0.05 or P < 0.01). Compared with the control group, the expression of genes involved in fatty acid synthesis increased significantly (P < 0.05 or P < 0.01), and the degrees of increase were proportional to the dose of 4-NP, as measured by lipoprotein lipase (Lpl), fatty acid synthetase (Fas), sterol regulatory element-binding protein 1 (Srebp-1) and peroxisome proliferator-activated receptor (Ppar)-γ. The expression of genes and proteins of ERα were changed significantly, as well (P < 0.05 or P < 0.01). The above changes in the liver tissues of F2 generation rats were consistent with the F1 generation rats. Conclusion: Perinatal exposure to 4-NP can affect the synthesis of fatty acid in the livers of F1 and F2 generation rats. The low expression of ERα may be one of the mechanisms by which 4-NP affected fatty acid synthesis in the livers of rats.

中文翻译：

---

围产期暴露于4-壬基苯酚会影响F1和F2代大鼠肝脏中的脂肪酸合成†

目的：探讨不同剂量的4-壬基酚（4-NP）对F1和F2大鼠肝脏脂肪酸合成和雌激素受体α（ERα）表达的影响。方法：将怀孕的大鼠随机分为四组：对照组，NP-5（每天每千克每天5微克），NP-25（每天每千克25微克）和NP-125（每天每千克125微克）。从妊娠第6天（GD）到出生后第21天（PND）取4-NP。将实验组的一些雌性大鼠与对照组的雄性大鼠交配以获得F2大鼠。杀死F1代大鼠（23周龄）和F2代大鼠（13周龄）以检测血液生化以及基因和蛋白质的表达。结果：与对照组相比，4-NP（NP-5，NP-25和NP-125）可以增加F1雄性后代的肝器官系数（P <0.05或P <0.01）。F1雌性NP-5组的高密度脂蛋白（HDL）浓度显着高于对照组（P <0.01）。其他指标没有改变，例如丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST），总胆固醇（TC）和低密度脂蛋白（LDL）。随着4-NP剂量的增加，血液生化的变化更为显着，尤其是在NP-125大鼠中（P <0.05或P <0.01）。肝活检组织病理学改变与血液生化指标一致（P <0.05或P <0.01）。与对照组相比，通过脂蛋白脂酶（Lpl）测定，参与脂肪酸合成的基因的表达显着增加（P <0.05或P <0.01），并且增加的程度与4-NP的剂量成正比。，脂肪酸合成酶（Fas），固醇调节元件结合蛋白1（Srebp-1）和过氧化物酶体增殖物激活受体（Ppar）-γ。ERα基因和蛋白质的表达也发生了显着变化（P <0.05或P<0.01）。F2代大鼠肝脏组织中的上述变化与F1代大鼠一致。结论：围产期暴露于4-NP会影响F1和F2代大鼠肝脏中脂肪酸的合成。ERα的低表达可能是4-NP影响大鼠肝脏脂肪酸合成的机制之一。