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Molecular basis of reduced birth weight in smoking pregnant women: mitochondrial dysfunction and apoptosis

机译:吸烟孕妇体重减轻的分子基础:线粒体功能障碍和细胞凋亡

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In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), newborn cord blood mononuclear cells (CBMCs) and placenta were collected from 30 smoking pregnant women and their newborns and classified as moderate and severe smoking groups, and compared to a cohort of 21 non-smoking controls. A biomarker for tobacco consumption (cotinine) was assessed by ELISA (enzyme-linked immunosorbent assay). The following parameters were measured in all tissues: mitochondrial chain complex IV [cytochrome c oxidase (COX)] activity by spectrophotometry, mitochondrial DNA levels by reverse transcription polymerase chain reaction, oxidative stress by spectrophotometric lipid peroxide quantification, mitochondrial mass through citrate synthase spectrophotometric activity and apoptosis by Western blot parallelly confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay in placenta. Newborns from smoking pregnant women presented reduced birth weight by 10.75 percent. Materno-fetal mitochondrial and apoptotic PBMC and CBMC parameters showed altered and correlated values regarding COX activity, mitochondrial DNA, oxidative stress and apoptosis. Placenta partially compensated this dysfunction by increasing mitochondrial number; even so ratios of oxidative stress and apoptosis were increased. A CO-induced mitotoxic and apoptotic fingerprint is present in smoking pregnant women and their newborn, with a lack of filtering effect from the placenta. Tobacco consumption correlated with a reduction in birth weight and mitochondrial and apoptotic impairment, suggesting that both could be the cause of the reduced birth weight in smoking pregnant women.
机译:子宫内胎儿暴露于烟草会降低出生体重。我们假设这可能是由于烟草中一氧化碳(CO)的毒性作用引起的,以前已经描述过这种作用会损害成年吸烟者的线粒体。从30名吸烟的孕妇及其新生儿中收集了孕妇外周血单核细胞(PBMC),新生儿脐带血单核细胞(CBMC)和胎盘,并将其分为中度和重度吸烟组,并与21名非吸烟对照组进行比较。通过ELISA(酶联免疫吸附测定)评估了烟草消费(烟碱)的生物标记。在所有组织中测量以下参数:通过分光光度法测定线粒体链复合物IV [细胞色素C氧化酶(COX)]活性,通过逆转录聚合酶链反应测定线粒体DNA水平,通过分光光度脂质过氧化物定量法测定氧化应激,通过柠檬酸合酶分光光度法测定线粒体质量胎盘中TUNEL(末端脱氧核苷酸转移酶dUTP缺口末端标记)法平行证实的Western blot检测细胞凋亡和凋亡。吸烟孕妇的新生儿出生体重减轻了10.75%。母胎的线粒体和凋亡PBMC和CBMC参数在COX活性,线粒体DNA,氧化应激和凋亡方面显示出变化和相关的值。胎盘通过增加线粒体数目来部分弥补这种功能障碍。即使如此,氧化应激和细胞凋亡的比率也增加了。吸烟的孕妇及其新生儿存在CO诱导的线粒体毒性和凋亡指纹,但缺乏胎盘的过滤作用。烟草消费与出生体重下降,线粒体和细胞凋亡受损有关,这两者都可能是吸烟孕妇出生体重下降的原因。

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