Sexually Dimorphic Modifications in Placental Cyclooxygeanse Metabolites After Maternal Nanomaterial Inhalation Exposure

Details

• Personal Author:
  Bowdridge EC ; Dunn AC ; Goldsmith WT ; Griffith JA ; Hussain S ; King RD ; Lewis SE ; Maxwell BA ; Nurkiewicz TR ; Wix K
• Description:
  Maternal nano-titanium dioxide (nano-TiO2) inhalation exposure during gestation results in decreased fetal female mass, maternal estrogen production, and placental mass. Placental function is critical during gestation due to its roles in nutrientwaste exchange and endocrine production. Adverse fetoplacental environments profoundly impact fetal growth and development. Additionally, the impacts of toxicant exposure can occur in a sexually dimorphic manner, which has been shown after maternal diesel exhaust exposure during gestation. Therefore, we hypothesized that maternal nano-TiO2 inhalation exposure during gestation alters placental function in a sexually dimorphic manner. Pregnant Sprague-Dawley rats were exposed to nano-TiO2 aerosols (12.17 +/- 1.69 mg/m3) or HEPA-filtered air (sham-control) from gestational day (GD) 10-19. Dams were euthanized on GD20, and placental junctional zone (JZ), labyrinth zone (LZ), and fetal serum were collected and separated based on fetal sex. Fetoplacental units, also based on fetal sex, nearest the cervix were removed, the umbilical vein and artery were separated and cut close to the pup. The placentas were then mounted in an isolated, perfused vessel chamber to assess outflow pressure and flow rate through the placenta in response to vasoactive drugs. The stable thromboxane and prostacyclin metabolites, TXB2 and 6-keto-PGF1á, respectively, were assessed in the JZ and LZ, and fetal serum using ELISA's. Nano-TiO2 exposed fetal females demonstrated significantly increased TXB2 production (11186.48 +/- 189.92 pg/ml) from LZ tissue compared to female sham-control (483.77 +/- 86.09 pg/ml) and male exposed (598.39 +/- 135.69 pg/ml). The JZ also had a significantly increased TXB2 levels in the exposed fetal females compared to exposed fetal males (1188.09 +/- 130.38 pg/ml vs 670.63 +/- 94.50 pg/ml, respectively) and sham-control females (649.25 +/- 143.27 pg/ml). Fetal exposed female serum 6-keto-PGF1á levels were significantly increased compared to exposed fetal males (97.56 +/- 25.86 pg/ml vs 16.33 +/- 4.44 pg/ml, respectively) and sham-control females (37.62 +/- 5.18 pg/ml). Placental outflow pressure was measured to assess perfused vascular resistance, in which, exposed fetal females demonstrated a significantly decreased outflow pressure (3.97 +/- 1.30 mm Hg) in the presence of the thromboxane mimetic, U46619, compared to sham-control fetal females (9.10 +/- 1.07 mm Hg) and nano-TiO2 exposed fetal males (9.96 +/- 0.66 mm Hg). Immunohistochemical staining was utilized to evaluate cytotrophoblast invasion, using the pan-cytokeratin marker, between placental zones. The JZ had significantly increased pan-cytokeratin intensity for sham-control males compared to females (67.24 +/- 5.21 AU vs 44.43 +/- 2.59 AU). The LZ pan-cytokeratin staining was decreased in sham-control females compared to males (64.65 +/- 7.47 AU vs 91.55 +/- 10.23 AU). The changes in placental hemodynamics and production of cyclooxygenase metabolites reflect a functional change that is occurring in the nano-TiO2 exposed fetal females. Modifications to cellular composition, as seen in staining, provides evidence there may also be changes in cellular composition leading to these functional changes. These results demonstrate that maternal nano-TiO2 inhalation exposure during gestation has greater impacts on fetal females and their placental units. [Description provided by NIOSH]
• Subjects:
  Aerosols Animals Occupational Health Pregnancy Respiratory System Safety Sex Characteristics Titanium
• Keywords:
  Animal Studies Inhalation Studies Nanoparticles Sex Factors Titanium Dioxide
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  192
• NIOSHTIC Number:
  nn:20067214
• Citation:
  Toxicologist 2023 Mar; 192(S1):211
• CAS Registry Number:
  Titania (CAS RN 13463-67-7)
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  West Virginia University
• Peer Reviewed:
  False
• Start Date:
  20220901
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• End Date:
  20250831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6b263cb17ca3f77100108f51bb68f8383cce3179411ccf474b44fd51ddb1a12b964f866fdf7adbe7ae1302b6338133b3b7ca6673a23fb561b389222a06caf2e5
• Download URL:
  https://stacks.cdc.gov/view/cdc/231341/cdc_231341_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]