PMID- 35066857 OWN - NLM STAT- MEDLINE DCOM- 20220301 LR - 20240226 IS - 1559-0259 (Electronic) IS - 1530-7905 (Print) IS - 1530-7905 (Linking) VI - 22 IP - 2 DP - 2022 Feb TI - Maternal Nanomaterial Inhalation Exposure: Critical Gestational Period in the Uterine Microcirculation is Angiotensin II Dependent. PG - 167-180 LID - 10.1007/s12012-021-09712-8 [doi] AB - Maternal inhalation exposure to engineered nanomaterials (ENM) has been associated with microvascular dysfunction and adverse cardiovascular responses. Pregnancy requires coordinated vascular adaptation and growth that are imperative for survival. Key events in pregnancy hallmark distinct periods of gestation such as implantation, spiral artery remodeling, placentation, and trophoblast invasion. Angiotensin II (Ang II) is a critical vasoactive mediator responsible for adaptations and is implicated in the pathology of preeclampsia. If perturbations occur during gestation, such as those caused by ENM inhalation exposure, then maternal-fetal health consequences may occur. Our study aimed to identify the period of gestation in which maternal microvascular functional and fetal health are most vulnerable. Additionally, we wanted to determine if Ang II sensitivity and receptor density is altered due to exposure. Dams were exposed to ENM aerosols (nano-titanium dioxide) during three gestational windows: early (EE, gestational day (GD) 2-6), mid (ME, GD 8-12) or late (LE, GD 15-19). Within the EE group dry pup mass decreased by 16.3% and uterine radial artery wall to lumen ratio (WLR) increased by 25.9%. Uterine radial artery response to Ang II sensitivity increased by 40.5% in the EE group. Ang II receptor density was altered in the EE and LE group with decreased levels of AT(2)R. We conclude that early gestational maternal inhalation exposures resulted in altered vascular anatomy and physiology. Exposure during this time-period results in altered vascular reactivity and changes to uterine radial artery WLR, leading to decreased perfusion to the fetus and resulting in lower pup mass. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Garner, Krista L AU - Garner KL AUID- ORCID: 0000-0003-4726-2991 AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Bowdridge, Elizabeth C AU - Bowdridge EC AUID- ORCID: 0000-0003-2183-1375 AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Griffith, Julie A AU - Griffith JA AUID- ORCID: 0000-0002-3863-2172 AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. FAU - DeVallance, Evan AU - DeVallance E AUID- ORCID: 0000-0003-0173-3188 AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Seman, Madison G AU - Seman MG AD - Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Engels, Kevin J AU - Engels KJ AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Groth, Caroline P AU - Groth CP AUID- ORCID: 0000-0001-9444-0207 AD - Department of Epidemiology and Biostatistics, West Virginia University School of Public Health, Morgantown, WV, USA. FAU - Goldsmith, William T AU - Goldsmith WT AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Wix, Kim AU - Wix K AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Batchelor, Thomas P AU - Batchelor TP AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. FAU - Nurkiewicz, Timothy R AU - Nurkiewicz TR AUID- ORCID: 0000-0001-9105-970X AD - Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA. tnurkiewicz@hsc.wvu.edu. AD - Center for Inhalation Toxicology (iTOX), West Virginia University School of Medicine, Morgantown, WV, USA. tnurkiewicz@hsc.wvu.edu. AD - Department of Physiology and Pharmacology, Robert C. Byrd Health Sciences Center, West Virginia University, 64 Medical Center Drive, Morgantown, WV, 26506-9229, USA. tnurkiewicz@hsc.wvu.edu. LA - eng GR - T32 ES032920/ES/NIEHS NIH HHS/United States GR - U54 GM104942/GM/NIGMS NIH HHS/United States GR - T32 AG052375/AG/NIA NIH HHS/United States GR - R01 ES015022/ES/NIEHS NIH HHS/United States GR - F32 HL152534/HL/NHLBI NIH HHS/United States GR - 5 T32 AG 52375-3/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20220123 PL - United States TA - Cardiovasc Toxicol JT - Cardiovascular toxicology JID - 101135818 RN - 0 (Aerosols) RN - 0 (Receptor, Angiotensin, Type 1) RN - 11128-99-7 (Angiotensin II) RN - 15FIX9V2JP (titanium dioxide) RN - 4TI98Z838E (Estradiol) RN - D1JT611TNE (Titanium) SB - IM MH - Aerosols MH - Angiotensin II/*pharmacology MH - Animals MH - Estradiol/blood MH - Female MH - Gestational Age MH - Inhalation Exposure MH - Maternal Exposure MH - Metal Nanoparticles/administration & dosage/*toxicity MH - *Microcirculation MH - *Placental Circulation MH - Pregnancy MH - Rats, Sprague-Dawley MH - Receptor, Angiotensin, Type 1/agonists/metabolism MH - Titanium/administration & dosage/*toxicity MH - Uterine Artery/*drug effects/physiopathology MH - Vasoconstriction/*drug effects MH - Rats PMC - PMC9013006 MID - NIHMS1791705 OTO - NOTNLM OT - Angiotensin II OT - Gestational inhalation exposure OT - Microcirculation OT - Titanium dioxide OT - Toxicology COIS- Conflict of interest The authors have no relevant financial or non-financial interests to disclose. EDAT- 2022/01/24 06:00 MHDA- 2022/03/03 06:00 PMCR- 2022/04/16 CRDT- 2022/01/23 20:38 PHST- 2021/10/07 00:00 [received] PHST- 2021/12/07 00:00 [accepted] PHST- 2022/01/24 06:00 [pubmed] PHST- 2022/03/03 06:00 [medline] PHST- 2022/01/23 20:38 [entrez] PHST- 2022/04/16 00:00 [pmc-release] AID - 10.1007/s12012-021-09712-8 [pii] AID - 10.1007/s12012-021-09712-8 [doi] PST - ppublish SO - Cardiovasc Toxicol. 2022 Feb;22(2):167-180. doi: 10.1007/s12012-021-09712-8. Epub 2022 Jan 23.