An animal model of cigarette smoke-induced in utero growth retardation
An animal model of cigarette smoke-induced in utero growth retardation
复制标题
DOI：
10.1016/j.tox.2008.01.014
复制
发表时间：
2008-04-18
期刊：
影响因子：
4.5
通讯作者：
Pisano, M. Michele
中科院分区：
文献类型：
--
作者：
Esposito, Emily R.;Horn, Kristin H.;Pisano, M. Michele
母体/胎儿的遗传素质和环境因素对于生出健康的婴儿至关重要。在美国 (US)，每分半钟就有一个低出生体重 (LBW) 婴儿出生。低出生体重（LBW）被定义为出生时体重低于 5.5 磅，在美国出生的 12 名婴儿中就有近 1 名受到影响，每年给国家造成的损失超过 150 亿美元。婴儿出生体重是影响新生儿死亡率的最重要因素。低出生体重的各种环境和遗传风险因素已被确定。有几种风险是可以预防的，例如怀孕期间吸烟。在美国，超过 100 万婴儿在产前接触过香烟烟雾，占 LBW 发病率的 20% 以上。子宫内接触香烟烟雾会导致各种不良发育结果，其中最有据可查的是宫内生长受限和婴儿低出生体重。然而，人们对低出生体重的潜在机制仍知之甚少。本研究的目的是：(1) 使用模拟“主动”和“被动”烟草烟雾暴露的生理相关吸入暴露条件，建立香烟烟雾引起的子宫内生长迟缓和低出生体重的动物模型，以及 (2) 确定特定的发育阶段是否比其他阶段更容易受到子宫内烟雾暴露对胚胎/胎儿生长的不利影响。怀孕的 C57BL/6J 小鼠在三个妊娠期暴露于香烟烟雾：植入前/围植入期（妊娠天数 [gds] 1-5）、植入后（gds 6-18）和整个妊娠期（gds 1-17）。生殖和胎儿结局在 18.5 日进行评估。将母鼠暴露于主流/侧流香烟烟雾中，模拟“主动”母亲吸烟，在整个妊娠期间暴露于主流/侧流香烟烟雾中，导致胎儿体重和头臀长度下降（gds 1-17）。当母鼠仅在妊娠前 5 天（着床前/围着床期 gds 1-5）暴露时，也出现了类似的结果。母鼠从着床后到妊娠期（gds 6-18）的暴露并没有导致胎儿体重减轻，尽管头臀长度的显着减少仍然很明显。有趣的是，在胚胎植入前/围植入期，母体侧流烟雾暴露（模拟环境烟草烟雾（ETS））也会导致胎儿体重和头臀长显着下降。总的来说，本研究的结果证实了产前接触“主动”或“被动”香烟烟雾与子宫内生长迟缓之间的关联。该数据还确定了在植入前/围植入期胚胎发育过程中对子宫内香烟烟雾暴露引起的生长迟缓和低出生体重的易感期。 (C) 2008 Elsevier Ireland Ltd. 保留所有权利。
Maternal/fetal genetic constitution and environmental factors are vital to delivery of a healthy baby. In the United States (US), a low birth weight (LBW) baby is born every minute and a half. LBW, defined as weighing less than 5.5 lbs at birth, affects nearly I in 12 infants born in the US with resultant costs for the nation of more than 15 billion dollars annually. Infant birth weight is the single most important factor affecting neonatal mortality. Various environmental and genetic risk factors for LBW have been identified. Several risks are preventable, such as cigarette smoking during pregnancy. Over one million babies are exposed prenatally to cigarette smoke accounting for over 20% of the LBW incidence in the US. Cigarette smoke exposure in utero results in a variety of adverse developmental outcomes with intrauterine growth restriction and infant LBW being the most well documented. However, the mechanisms underlying the causes of LBW remain poorly understood. The purpose of this study was: (1) to establish an animal model of cigarette smoke-induced in utero growth retardation and LBW using physiologically relevant inhalation exposure conditions which simulate "active" and "passive" tobacco smoke exposures, and (2) to determine whether particular stages of development are more susceptible than others to the adverse effects of in utero smoke exposure on embryo/fetal growth. Pregnant C57BL/6J mice were exposed to cigarette smoke during three periods of gestation: pre-/peri-implantation (gestational days [gds] 1-5), post-implantation (gds 6-18), and throughout gestation (gds 1-17). Reproductive and fetal outcomes were assessed on gd 18.5. Exposure of dams to mainstream/sidestream cigarette smoke, simulating "active" maternal smoking, resulted in decreases in fetal weight and crown-rump length when exposed throughout gestation (gds 1-17). Similar results were seen when dams were exposed only during the first 5 days of gestation (pre-/peri-implantation period gds 1-5). Exposure of dams from the post-implantation period through gestation (gds 6-18) did not result in reduced fetal weight, although a significant reduction in crown-rump length remained evident. Interestingly, maternal sidestream smoke exposure, simulating exposure to environmental tobacco smoke (ETS), during the pre-/peri-implantation period of development also produced significant decreases in fetal weight and crown-rump length. Collectively, results from the present study confirm an association between prenatal exposure to either "active" or "passive" cigarette smoke and in utero growth retardation. The data also identify a period of susceptibility to in utero cigarette smoke exposure-induced growth retardation and LBW during pre-/peri-implantation embryonic development. (C) 2008 Elsevier Ireland Ltd. All rights reserved.