孕前和孕期母鼠低硒饲料喂养对胎鼠生长发育的损害作用
|
摘要
[目的]孕期母体硒缺乏导致胎儿生长受限的发生风险升高目前尚存在争议,本研究旨在从动物实验中探讨孕前和孕期母鼠低硒饲料喂养对胎鼠生长发育的影响及其相关机制。[方法]40只3周ICR雌鼠被随机分为对照组和低硒组各20只,对照组与低硒组分别喂养维持饲料(硒质量分数为0.18 mg/kg)和低硒饲料(硒质量分数为0.02 mg/kg),连续喂养8周后与正常雄鼠交配,孕鼠继续分组喂养至受孕第18天,然后剖杀孕鼠,评价胎鼠生长发育情况,收集母鼠、胎鼠血清和胎盘,用石墨炉原子吸收法检测血清硒质量浓度,用定量RT-PCR方法检测胎盘Cat、Sod1和Sod2 m RNA水平,用免疫组化和Western blot方法检测胎盘3-硝基酪氨酸(3-NT)表达。所有计量资料用均数±标准差■来描述,采用t检验进行两组之间比较。[结果]在孕前和孕期阶段,低硒组和对照组母鼠总进食量和体重增长之间差异均无统计学意义(P>0.05)。硒质量浓度检测结果显示,对照组孕鼠和胎鼠血清硒质量浓度分别为(121.7±43.0)和(79.5±30.8)μg/L,低硒组孕鼠和胎鼠血清硒质量浓度分别为(74.6±34.7)和(36.2±26.0)μg/L,低硒组孕鼠血清和胎鼠血清硒质量浓度均低于对照组(P<0.05)。生长发育检查结果表明,对照组胎鼠体重为(1.38±0.08)g,低硒组胎鼠体重为(1.31±0.06)g,低硒组胎鼠体重低于对照组(P<0.05)。定量RT-PCR结果显示,低硒组与对照组胎盘组织Cat、Sod1和Sod2 mRNA水平之间差异均无统计学意义(P>0.05)。免疫组织化学结果显示,低硒组小鼠胎盘组织3-NT阳性细胞数高于对照组(P<0.05)。Western blot结果显示,低硒组小鼠胎盘组织3-NT蛋白表达水平高于对照组(P<0.05)。[结论]孕前和孕期母鼠低硒饲料喂养引起胎鼠生长受限,可能与胎盘氧化应激反应有关。
[Objective] Whether maternal selenium deficiency during gestation elevates the risk for fetal growth restriction(FGR) remains controversial. The present study is to explore the adverse effects of maternal exposure to low selenium diet before and during pregnancy on the growth and development of mouse fetuses and related potential mechanisms.[Methods] Forty ICR female mice(three weeks old) were randomly divided into a control diet(CD) group(0.18 mg/kg selenium) and a low selenium diet(LSD) group(0.02 mg/kg selenium), with 20 mice in each group. Females and males were mated after eight weeks of feeding, and the pregnant mice were fed with the same diet as before until being sacrificed on gestational day(GD) 18. Growth and development of mouse fetuses were evaluated. Maternal and fetal mice serum and placenta samples were collected to detect serum selenium(Se) concentration by graphite furnace atomic absorption spectrometry, the mRNA expression levels of Cat, Sod1, and Sod2 in placenta by quantitative RT-PCR, and 3-nitrotyrosine(3-NT) expression level in placenta by immunohistochemistry and Western blot. All measurement data were presented as mean±SD and analyzed by t test.[Results] No significant differences were observed in total food intake and weight gain between the CD and LSD groups before and during pregnancy(P >0.05). The serum selenium levels of pregnant mice and fetal mice were(121.7±43.0) and(79.5±30.8) μg/L in the CD group and(74.6±34.7) and(36.2±26.0) μg/L in the LSD group; the LSD group had significantly lower pregnant and fetal serum selenium levels than the CD group(P< 0.05). The examination results of growth and development showed that the fetal weight was(1.38±0.08) g in the CD group and(1.31±0.06) g in the LSD group; the LSD group had a significantly lower fetal weight than the CD group(P< 0.05). The results of quantitative RT-PCR showed no differences between the LSD group and the CD group in the mR NA expression levels of Cat, Sod1, and Sod2(P >0.05). Moreover, the results from immunostaining and Western blot showed that the 3-NT positive cells and protein expression levels in the LSD-exposed mice were significantly higher than those in the CD-exposed mice(P< 0.05). [Conclusion] Maternal exposure to low selenium diet before and during pregnancy could induce fetal growth restriction and the latter may be associated with placental oxidative stress.
[Objective] Whether maternal selenium deficiency during gestation elevates the risk for fetal growth restriction(FGR) remains controversial. The present study is to explore the adverse effects of maternal exposure to low selenium diet before and during pregnancy on the growth and development of mouse fetuses and related potential mechanisms.[Methods] Forty ICR female mice(three weeks old) were randomly divided into a control diet(CD) group(0.18 mg/kg selenium) and a low selenium diet(LSD) group(0.02 mg/kg selenium), with 20 mice in each group. Females and males were mated after eight weeks of feeding, and the pregnant mice were fed with the same diet as before until being sacrificed on gestational day(GD) 18. Growth and development of mouse fetuses were evaluated. Maternal and fetal mice serum and placenta samples were collected to detect serum selenium(Se) concentration by graphite furnace atomic absorption spectrometry, the mRNA expression levels of Cat, Sod1, and Sod2 in placenta by quantitative RT-PCR, and 3-nitrotyrosine(3-NT) expression level in placenta by immunohistochemistry and Western blot. All measurement data were presented as mean±SD and analyzed by t test.[Results] No significant differences were observed in total food intake and weight gain between the CD and LSD groups before and during pregnancy(P >0.05). The serum selenium levels of pregnant mice and fetal mice were(121.7±43.0) and(79.5±30.8) μg/L in the CD group and(74.6±34.7) and(36.2±26.0) μg/L in the LSD group; the LSD group had significantly lower pregnant and fetal serum selenium levels than the CD group(P< 0.05). The examination results of growth and development showed that the fetal weight was(1.38±0.08) g in the CD group and(1.31±0.06) g in the LSD group; the LSD group had a significantly lower fetal weight than the CD group(P< 0.05). The results of quantitative RT-PCR showed no differences between the LSD group and the CD group in the mR NA expression levels of Cat, Sod1, and Sod2(P >0.05). Moreover, the results from immunostaining and Western blot showed that the 3-NT positive cells and protein expression levels in the LSD-exposed mice were significantly higher than those in the CD-exposed mice(P< 0.05). [Conclusion] Maternal exposure to low selenium diet before and during pregnancy could induce fetal growth restriction and the latter may be associated with placental oxidative stress.
引文
[1]STRANGES S,GALLETTI F,FARINARO E,et al.Associations of selenium status with cardiometabolic risk factors:an8-year follow-up analysis of the Olivetti Heart Study[J].Atherosclerosis,2011,217(1):274-278.
[2]NAVARRO-ALARCóN M,LóPEZ-MARTíNEZ M C.Essentiality of selenium in the human body:relationship with different diseases[J].Sci Total Environ,2000,249(1/2/3):347-371.
[3]彭大明.中国硒矿资源概述[J].化工矿产地质,1997,19(1):36-42.
[4]王晓玲.微量元素硒在人体内的作用[J].中国地方病防治杂志,2009,24(6):420-422.
[5]RENKO K,HOFMANN P J,STOEDTER M,et al.Downregulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice[J].FASEB J,2009,23(6):1758-1765.
[6]SOBIECKI J G.Vegetarianism and colorectal cancer risk in a low-selenium environment:effect modification by selenium status?A possible factor contributing to the null results in British vegetarians[J].Eur J Nutr,2017,56(5):1819-1832.
[7]侯振江,张宗英,闫瑞霞.硒的生物学特性及其在肿瘤诊疗中的应用[J].微量元素与健康研究,2003,20(4):11-13.
[8]TSUZUKI S,MORIMOTO N,HOSOKAWA S,et al.Associations of maternal and neonatal serum trace element concentrations with neonatal birth weight[J].PLoS One,2013,8(9):e75627.
[9]BOGDEN J D,KEMP F W,CHEN X,et al.Low-normal serum selenium early in human pregnancy predicts lower birth weight[J].Nutr Res,2006,26(10):497-502.
[10]NAZEMI L,SHARIAT M,CHAMARI M,et al.Comparison of maternal and umbilical cord blood selenium levels in low and normal birth weight neonates[J].J Family Reprod Health,2015,9(3):125-128.
[11]NOGALES F,OJEDA M L,FENUTRíA M,et al.Role of selenium and glutathione peroxidase on development,growth,and oxidative balance in rat offspring[J].Reproduction,2013,146(6):659-667.
[12]ARTHUR J R,BECKETT G J.Some biochemical functions of selenium in animals and man[M]//ROUSSEL A M,ANDERSON R A,FAVRIER A E.Trace Elements in Man and Animals 10.Boston,MA:Springer,2002:843-847.
[13]JAUNIAUX E,BURTON G J.The role of oxidative stress in placental-related diseases of pregnancy[J].J Gynecol Obstet Biol Reprod(Paris),2016,45(8):775-785.
[14]LIN F,YU X,ZHANG X,et al.A synthetic analog of lipoxin A4 partially alleviates dexamethasone-induced fetal growth restriction in rats[J].Placenta,2013,34(10):941-948.
[15]王华.孕期母体镉暴露与胎儿生长受限的关联及其机制研究[D].合肥:安徽医科大学,2015.
[16]PETERS B,BALLMANN C,QUINDRY T,et al.Experimental woodsmoke exposure during exercise and blood oxidative stress[J].J Occup Environ Med,2018,60(12):1073-1081.
[17]谢香荣.人血清硫氧还蛋白、3-硝基酪氨酸与糖尿病视网膜病变相关性研究[D].太原:山西医科大学,2013.
[2]NAVARRO-ALARCóN M,LóPEZ-MARTíNEZ M C.Essentiality of selenium in the human body:relationship with different diseases[J].Sci Total Environ,2000,249(1/2/3):347-371.
[3]彭大明.中国硒矿资源概述[J].化工矿产地质,1997,19(1):36-42.
[4]王晓玲.微量元素硒在人体内的作用[J].中国地方病防治杂志,2009,24(6):420-422.
[5]RENKO K,HOFMANN P J,STOEDTER M,et al.Downregulation of the hepatic selenoprotein biosynthesis machinery impairs selenium metabolism during the acute phase response in mice[J].FASEB J,2009,23(6):1758-1765.
[6]SOBIECKI J G.Vegetarianism and colorectal cancer risk in a low-selenium environment:effect modification by selenium status?A possible factor contributing to the null results in British vegetarians[J].Eur J Nutr,2017,56(5):1819-1832.
[7]侯振江,张宗英,闫瑞霞.硒的生物学特性及其在肿瘤诊疗中的应用[J].微量元素与健康研究,2003,20(4):11-13.
[8]TSUZUKI S,MORIMOTO N,HOSOKAWA S,et al.Associations of maternal and neonatal serum trace element concentrations with neonatal birth weight[J].PLoS One,2013,8(9):e75627.
[9]BOGDEN J D,KEMP F W,CHEN X,et al.Low-normal serum selenium early in human pregnancy predicts lower birth weight[J].Nutr Res,2006,26(10):497-502.
[10]NAZEMI L,SHARIAT M,CHAMARI M,et al.Comparison of maternal and umbilical cord blood selenium levels in low and normal birth weight neonates[J].J Family Reprod Health,2015,9(3):125-128.
[11]NOGALES F,OJEDA M L,FENUTRíA M,et al.Role of selenium and glutathione peroxidase on development,growth,and oxidative balance in rat offspring[J].Reproduction,2013,146(6):659-667.
[12]ARTHUR J R,BECKETT G J.Some biochemical functions of selenium in animals and man[M]//ROUSSEL A M,ANDERSON R A,FAVRIER A E.Trace Elements in Man and Animals 10.Boston,MA:Springer,2002:843-847.
[13]JAUNIAUX E,BURTON G J.The role of oxidative stress in placental-related diseases of pregnancy[J].J Gynecol Obstet Biol Reprod(Paris),2016,45(8):775-785.
[14]LIN F,YU X,ZHANG X,et al.A synthetic analog of lipoxin A4 partially alleviates dexamethasone-induced fetal growth restriction in rats[J].Placenta,2013,34(10):941-948.
[15]王华.孕期母体镉暴露与胎儿生长受限的关联及其机制研究[D].合肥:安徽医科大学,2015.
[16]PETERS B,BALLMANN C,QUINDRY T,et al.Experimental woodsmoke exposure during exercise and blood oxidative stress[J].J Occup Environ Med,2018,60(12):1073-1081.
[17]谢香荣.人血清硫氧还蛋白、3-硝基酪氨酸与糖尿病视网膜病变相关性研究[D].太原:山西医科大学,2013.