Center for Cardiovascular and Respiratory Sciences and Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506-9105, USA.
Am J Obstet Gynecol. 2013 Sep;209(3):227.e1-11. doi: 10.1016/j.ajog.2013.04.036. Epub 2013 Apr 30.
The continued development and use of engineered nanomaterials (ENM) has given rise to concerns over the potential for human health effects. Although the understanding of cardiovascular ENM toxicity is improving, one of the most complex and acutely demanding "special" circulations is the enhanced maternal system to support fetal development. The Barker hypothesis proposes that fetal development within a hostile gestational environment may predispose/program future sensitivity. Therefore, the objective of this study was 2-fold: (1) to determine whether maternal ENM exposure alters uterine and/or fetal microvascular function and (2) test the Barker hypothesis at the microvascular level.
Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide aerosols (11.3 ± 0.039 mg/m(3)/hr, 5 hr/d, 8.2 ± 0.85 days) to evaluate the maternal and fetal microvascular consequences of maternal exposure. Microvascular tissue isolation (gestation day 20) and arteriolar reactivity studies (<150 μm passive diameter) of the uterine premyometrial and fetal tail arteries were conducted.
ENM exposures led to significant maternal and fetal microvascular dysfunction, which was seen as robustly compromised endothelium-dependent and -independent reactivity to pharmacologic and mechanical stimuli. Isolated maternal uterine arteriolar reactivity was consistent with a metabolically impaired profile and hostile gestational environment that impacted fetal weight. The fetal microvessels that were isolated from exposed dams demonstrated significant impairments to signals of vasodilation specific to mechanistic signaling and shear stress.
To our knowledge, this is the first report to provide evidence that maternal ENM inhalation is capable of influencing fetal health and that the Barker hypothesis is applicable at the microvascular level.
工程纳米材料（ENM）的持续发展和应用引起了人们对其潜在人类健康影响的关注。尽管人们对心血管 ENM 毒性的认识在不断提高，但其中最复杂和最苛刻的“特殊”循环之一是增强的母体系统以支持胎儿发育。Barker 假说提出，在恶劣的妊娠环境中胎儿的发育可能会导致未来的敏感性。因此，本研究的目的有两个：（1）确定母体 ENM 暴露是否改变子宫和/或胎儿微血管功能；（2）在微血管水平上验证 Barker 假说。
将怀孕（妊娠第 10 天）的 Sprague-Dawley 大鼠暴露于纳米二氧化钛气溶胶中（11.3 ± 0.039 mg/m3/小时，5 小时/天，8.2 ± 0.85 天），以评估母体和胎儿微血管暴露对母体的影响。进行微血管组织分离（妊娠第 20 天）和子宫前肌层和胎儿尾动脉的小动脉反应性研究（<150 μm 被动直径）。
ENM 暴露导致明显的母体和胎儿微血管功能障碍，表现为对药物和机械刺激的内皮依赖性和非依赖性反应明显受损。分离的母体子宫小动脉反应性与代谢受损的特征一致，并且妊娠环境恶劣，这影响了胎儿的体重。从暴露的母鼠中分离出的胎儿微血管表现出对特定于机械信号和切应力的血管扩张信号的显著损伤。
据我们所知，这是第一项提供证据表明母体吸入 ENM 能够影响胎儿健康的报告，并且 Barker 假说适用于微血管水平。
