Maternal Engineered Nanomaterial Inhalation During Gestation Disrupts Vascular Kisspeptin Reactivity

Details

• Personal Author:
  Abukabda AB ; Batchelor TP ; Bowdridge EC ; Engles KJ ; Friend S ; Garner KL ; Goldsmith WT ; McBride CR ; Nurkiewicz TR
• Description:
  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 µg; 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 × 10-9 to 1?×?10-4 M). Estrogen was decreased at GD 20 in exposed (11.08+/-3 pg/mL) vs. 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) vs. 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. [Description provided by NIOSH]
• Subjects:
  Aerosols Animals Environmental Exposure Estrogens Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Titanium Urogenital System

  More +
• Keywords:
  Author Keywords: Engineered Nanomaterials Exposure Levels Inhalation Kisspeptin Laboratory Animals Microcirculation Nanomaterials Placenta Progesterone Pulmonary Effects Pulmonary System Pulmonary System Disorders Risk Factors Titanium Dioxide Uterus

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  169
• Issue:
  2
• NIOSHTIC Number:
  nn:20055104
• Citation:
  Toxicol Sci 2019 Jun; 169(2):524-533
• Contact Point Address:
  Timothy R. Nurkiewicz, Ph.D., Department of Physiology and Pharmacology, 64 Medical Center Drive, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, 26505-9229
• Email:
  tnurkiewicz@hsc.wvu.edu
• Federal Fiscal Year:
  2019
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1af1ca06ce10aaf7364ef6a18c30d8fd2c3f3f375f049339190d604b5ab35fc8b0a5f1e30500c6b8a75c79abfa7eacdf779a293032e492f8baf24db6c1cc42ce
• Download URL:
  https://stacks.cdc.gov/view/cdc/217473/cdc_217473_DS1.pdf
• File Type:
  [PDF - 749.95 KB ]