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The Transgenerational Effects of Maternal Nano-TiO2 Inhalation

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  • Personal Author:
  • Description:
    Background and Purpose: According to the developmental origins of health and disease, a compromised in utero environment is detrimental to fetal development and long-term adult health outcomes. Past research in our laboratory has shown maternal toxicant inhalation deteriorates placental function and fetal health. The aim of this study was to determine the effects of nano-titanium dioxide (nano-TiO2) inhalation on endocrine and reproductive outcomes as well as transgenerational outcomes in F0-F4 progeny. Methods: Pregnant Sprague Dawley rats were exposed from gestational day (GD) 10- 19 to nano-TiO2 (12.35+/-0.13 mg/m3/6h/6d) or filtered air (sham-control). Dam weight was recorded before each exposure as an indicator of pregnancy maintenance and health. F0-F3 dams were euthanized on GD 20. Dams and neonates were weighed for tissue collection. Endocrine disruption was analyzed by competitive binding enzyme-linked immunosorbent assay (ELISA) for maternal plasma for E2. Ovarian and uterine tissue were analyzed for mRNA and protein analysis of estrogen. Placentas and fetuses were processed for reverse-transcription polymerase chain reaction (RT- qPCR) for 3BHSD, 17BHSD, StAR, and SRY detection. Results: F1- F3 litter size was significantly reduced when born to exposed dams compared to sham- controls. F1 placental tissue was found to express 17BHSD and was significantly lower when born to exposed dams (P < 0.05). Additionally, not only was circulating estrogen was significantly decreased at GD 20 in exposed F0 dams (11.08+/-3.0 pg/ml) versus sham-control dams (66.97+/-3.0 pg/ml), but also in F1 dams with exposed mothers (12.12+/-3.1 pg/ml) versus dams with shamcontrol mothers (29.81+/-8.8 pg/ml). F2-F3 statistical significance could not be determined. Pup wet weight and placental efficiency were significantly reduced in F2 and F3 litters born to exposed dams when compared to sham-control. Interestingly, there was no statistical significance between F4 litter size (13.1+/-0.88 vs. 12.67+/-0.60) or fetal wet weight (4.12+/-0.05 vs. 4.13+/-0.04) between groups. However, placental efficiency was significantly reduced in F4 litters born in exposed dams compared to shamcontrols. Conclusions: These data lay the groundwork for future research focusing on estrogen signaling in F2-F4 generations and determining downstream signaling pathways. Identifying the mechanisms by which nanomaterial exposure adversely affects maternal and fetal health not only contributes to overall health, but also has direct implications for public health and workplace safety. With a particular focus on occupational settings, where exposure to toxicants may be prevalent, the project sheds light on the potential risks faced by individuals of reproductive age, advocating for informed decision-making, awareness, and the development of safer work environments. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1096-6080
  • Document Type:
  • Genre:
  • Place as Subject:
  • CIO:
  • Division:
  • Topic:
  • Location:
  • Pages in Document:
    102-103
  • Volume:
    198
  • NIOSHTIC Number:
    nn:20069369
  • Citation:
    Toxicologist 2024 Mar; 198(S2):102-103
  • CAS Registry Number:
  • Federal Fiscal Year:
    2024
  • NORA Priority Area:
  • Peer Reviewed:
    False
  • Source Full Name:
    The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:d7b57748c73a750524b583a015ee6d0f9cc1a731c40000c04f53d2f0d282a0a4a0a6695e6a9e505cb775361c17f358fc22dc833a13bb41058c6fa5b9767a33a0
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  • File Type:
    Filetype[PDF - 4.39 MB ]
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