Objective
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.
Study Design
Pregnant (gestation day 10) Sprague-Dawley rats were exposed to nano-titanium dioxide
aerosols (11.3 ± 0.039 mg/m3/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.
Results
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.
Conclusion
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.
Key words
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Article info
Publication history
Published online: May 02, 2013
Accepted:
April 29,
2013
Received in revised form:
April 1,
2013
Received:
January 17,
2013
Footnotes
Supported by grant numbers F32-ES023435 (P.A.S.), R01-ES015022 (T.R.N.), and RC1-ES018274 (T.R.N.) from the National Institute of Health, National Science Foundation grant number 1003907 (T.R.N. and V.C.M.), and National Science Foundation Cooperative Agreement number EPS-1003907.
The authors report no conflict of interest.
Cite this article as: Stapleton PA, Minarchick VC, Yi J, et al. Maternal engineered nanomaterial exposure and fetal microvascular function: does the Barker hypothesis apply? Am J Obstet Gynecol 2013;209:227.e1-11.
Identification
Copyright
© 2013 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
