PMID- 30843041
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200601
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 169
IP  - 2
DP  - 2019 Jun 1
TI  - Maternal Engineered Nanomaterial Inhalation During Gestation Disrupts Vascular 
      Kisspeptin Reactivity.
PG  - 524-533
LID - 10.1093/toxsci/kfz064 [doi]
AB  - Maternal engineered nanomaterial (ENM) inhalation is associated with uterine 
      vascular impairments and endocrine disruption that may lead to altered 
      gestational outcomes. We have shown that nano-titanium dioxide (nano-TiO2) 
      inhalation impairs endothelium-dependent uterine arteriolar dilation in pregnant 
      rats. However, the mechanism underlying this dysfunction is unknown. Due to its 
      role as a potent vasoconstrictor and essential reproductive hormone, we examined 
      how kisspeptin is involved in nano-TiO2-induced vascular dysfunction and 
      placental efficiency. Pregnant Sprague Dawley rats were exposed (gestational day 
      [GD] 10) to nano-TiO2 aerosols (cumulative dose = 525 +/- 16 mug; n = 8) or sham 
      exposed (n = 6) and sacrificed on GD 20. Plasma was collected to evaluate 
      estrogen (E2), progesterone (P4), prolactin (PRL), corticosterone (CORT), and 
      kisspeptin. Pup and placental weights were measured to calculate placental 
      efficiency (grams fetus/gram placental). Additionally, pressure myography was 
      used to determine uterine artery vascular reactivity. Contractile responses were 
      assessed via cumulative additions of kisspeptin (1 x 10-9 to 1 x 10-4 M). 
      Estrogen was decreased at GD 20 in exposed (11.08 +/- 3 pg/ml) versus sham-control 
      rats (66.97 +/- 3 pg/ml), whereas there were no differences in P4, PRL, CORT, or 
      kisspeptin. Placental weights were increased in exposed (0.99 +/- 0.03 g) versus 
      sham-control rats (0.70 +/- 0.04 g), whereas pup weights (4.01 +/- 0.47 g vs 
      4.15 +/- 0.15 g) and placental efficiency (4.5 +/- 0.2 vs 6.4 +/- 0.5) were decreased 
      in exposed rats. Maternal ENM inhalation exposure augmented uterine artery 
      vasoconstrictor responses to kisspeptin (91.2%+/-2.0 vs 98.6%+/-0.10). These studies 
      represent initial evidence that pulmonary maternal ENM exposure perturbs the 
      normal gestational endocrine vascular axis via a kisspeptin-dependent mechanism, 
      and decreased placental, which may adversely affect health outcomes.
CI  - Published by Oxford University Press on behalf of the Society of Toxicology 2019.
FAU - Bowdridge, Elizabeth C
AU  - Bowdridge EC
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
FAU - Abukabda, Alaeddin B
AU  - Abukabda AB
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
FAU - Engles, Kevin J
AU  - Engles KJ
AD  - Department of Physiology and Pharmacology.
FAU - McBride, Carroll R
AU  - McBride CR
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
FAU - Batchelor, Thomas P
AU  - Batchelor TP
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
FAU - Goldsmith, William T
AU  - Goldsmith WT
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
FAU - Garner, Krista L
AU  - Garner KL
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
FAU - Friend, Sherri
AU  - Friend S
AD  - Health Effects Laboratory Division, National Institute for Occupational Safety 
      and Health, Morgantown 26505, West Virginia.
FAU - Nurkiewicz, Timothy R
AU  - Nurkiewicz TR
AD  - Department of Physiology and Pharmacology.
AD  - Center for Inhalation Toxicology, Toxicology Working Group, West Virginia 
      University School of Medicine, 26506.
AD  - Health Effects Laboratory Division, National Institute for Occupational Safety 
      and Health, Morgantown 26505, West Virginia.
LA  - eng
GR  - P20 RR016440/RR/NCRR NIH HHS/United States
GR  - P30 GM103488/GM/NIGMS NIH HHS/United States
GR  - P30 RR032138/RR/NCRR NIH HHS/United States
GR  - R01 ES015022/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Gonadal Steroid Hormones)
RN  - 0 (Kisspeptins)
RN  - 15FIX9V2JP (titanium dioxide)
RN  - D1JT611TNE (Titanium)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fetus/*drug effects
MH  - Gonadal Steroid Hormones/blood
MH  - Inhalation Exposure
MH  - Kisspeptins/blood/*physiology
MH  - Maternal Exposure/*adverse effects
MH  - Nanoparticles
MH  - Placenta/drug effects/pathology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Titanium/*toxicity
MH  - Uterine Artery/*drug effects/physiology
PMC - PMC6542330
OTO - NOTNLM
OT  - engineered nanomaterials
OT  - kisspeptin
OT  - microcirculation
OT  - placenta
OT  - titanium dioxide
EDAT- 2019/03/08 06:00
MHDA- 2020/05/06 06:00
PMCR- 2020/06/01
CRDT- 2019/03/08 06:00
PHST- 2019/03/08 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2019/03/08 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - 5370552 [pii]
AID - kfz064 [pii]
AID - 10.1093/toxsci/kfz064 [doi]
PST - ppublish
SO  - Toxicol Sci. 2019 Jun 1;169(2):524-533. doi: 10.1093/toxsci/kfz064.