Prenatal Exposure to a Low Dose of BPS Causes Sex-Dependent Alterations to Vascular Endothelial Function in Adult Offspring
| dc.contributor.advisor | Thompson, Jennifer | |
| dc.contributor.advisor | Cole, William | |
| dc.contributor.author | Connors, Liam | |
| dc.contributor.committeemember | Habibi, Hamid | |
| dc.contributor.committeemember | Ahmed, Sofia | |
| dc.date | 2022-11 | |
| dc.date.accessioned | 2022-07-05T17:38:03Z | |
| dc.date.available | 2022-07-05T17:38:03Z | |
| dc.date.issued | 2022-06 | |
| dc.description.abstract | Background: Bisphenol A (BPA) is among the world’s most ubiquitous industrial chemicals, used as a plasticizer in the manufacture of plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular function through stimulation of nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS). After regulatory agencies declared BPA to be a toxic substance in 2010, manufacturers turned to substitutes such as bisphenol S (BPS). BPS can cross into the placenta, and it accumulates in the fetal compartment to a greater extent than BPA, potentially interfering with key developmental events. Little is known regarding the developmental impact of exposure to BPA analogues, particularly with respect to vascular development and later-life vascular function. Objective: To determine if prenatal BPS exposure influences vascular health in adulthood through modulation of NO production. Methods: Mesenteric arteries were excised from 12-week-old male and female C57BL/6 mice prenatally exposed to 250 nM BPS and mounted on a pressure myograph. Contractile and dilatory function was assessed by generating concentration-response curves to phenylephrine (Phe) and the endothelium-dependent dilator, acetylcholine (ACh). Wire myography was used to assess dilatory responses of aortic rings after acute exposure to BPS in the bath in the presence or absence of pharmacological inhibitors of eNOS and ER. Results: Vessels isolated from prenatally-exposed males did not exhibit changes in their dilatory or contractile responses. Whereas increased ACh dilation and increased sensitivity to Phe were observed in microvessels from female BPS-exposed mice. The increase in dilation was blocked by inhibition of eNOS. Aortic rings isolated from female mice and acutely exposed to BPS had increased dilatory responses to ACh that were eliminated with inhibition of eNOS or ER. Conclusions: Prenatal BPS exposure leads to endothelium-dependent alterations of vascular function in a sex-specific manner that appears to be modulated by interaction with ER. | en_US |
| dc.identifier.citation | Connors, L. (2022). Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/39876 | |
| dc.identifier.uri | http://hdl.handle.net/1880/114806 | |
| dc.language.iso | eng | en_US |
| dc.publisher.faculty | Cumming School of Medicine | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject | Development | en_US |
| dc.subject | Fetal programming | en_US |
| dc.subject | Bisphenols | en_US |
| dc.subject | Vasculature | en_US |
| dc.subject | Endothelium | en_US |
| dc.subject.classification | Pathology | en_US |
| dc.subject.classification | Pharmacology | en_US |
| dc.subject.classification | Toxicology | en_US |
| dc.title | Prenatal Exposure to a Low Dose of BPS Causes Sex-Dependent Alterations to Vascular Endothelial Function in Adult Offspring | en_US |
| dc.type | master thesis | en_US |
| thesis.degree.discipline | Medicine – Cardiovascular/Respiratory Science | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Master of Science (MSc) | en_US |
| ucalgary.item.requestcopy | true | en_US |