Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring
Background: Bisphenol S (BPS) is among the most commonly used substitutes for Bisphenol A (BPA), an endocrine disrupting chemical used as a plasticizer in the manufacture of polycarbonate plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Toxicology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/ftox.2022.933572/full |
| _version_ | 1811342104457117696 |
|---|---|
| author | Liam T. Connors Liam T. Connors Liam T. Connors Hai-Lei Zhu Hai-Lei Zhu Manvir Gill Emma Walsh Emma Walsh Radha D. Singh Radha D. Singh Radha D. Singh Radha D. Singh Sarah Easson Sarah Easson Sarah Easson Sofia B. Ahmed Sofia B. Ahmed Hamid R. Habibi William C. Cole William C. Cole William C. Cole Jennifer A. Thompson Jennifer A. Thompson Jennifer A. Thompson Jennifer A. Thompson |
| author_facet | Liam T. Connors Liam T. Connors Liam T. Connors Hai-Lei Zhu Hai-Lei Zhu Manvir Gill Emma Walsh Emma Walsh Radha D. Singh Radha D. Singh Radha D. Singh Radha D. Singh Sarah Easson Sarah Easson Sarah Easson Sofia B. Ahmed Sofia B. Ahmed Hamid R. Habibi William C. Cole William C. Cole William C. Cole Jennifer A. Thompson Jennifer A. Thompson Jennifer A. Thompson Jennifer A. Thompson |
| author_sort | Liam T. Connors |
| collection | DOAJ |
| description | Background: Bisphenol S (BPS) is among the most commonly used substitutes for Bisphenol A (BPA), an endocrine disrupting chemical used as a plasticizer in the manufacture of polycarbonate plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular function through stimulation of nitric oxide (NO) production via endothelial nitric oxide synthase (eNOS). BPS can cross into the placenta and 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 substitutes, particularly with respect to the vasculature.Objective: To determine if prenatal BPS exposure influences vascular health in adulthood.Methods: At the time of mating, female C57BL/6 dams were administered BPS (250 nM) or vehicle control in the drinking water, and exposure continued during lactation. At 12-week of age, mesenteric arteries were excised from male and female offspring and assessed for responses to an endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) vasodilator. Endothelium-dependent dilation was measured in the presence or absence of L-NAME, an eNOS inhibitor. To further explore the role of NO and ER signaling, wire myography was used to assess ACh responses in aortic rings after acute exposure to BPS in the presence or absence of L-NAME or an ER antagonist.Results: Increased ACh dilation and increased sensitivity to Phe were observed in microvessels from BPS-exposed females, while no changes were observed in male offspring. Differences in ACh-induced dilation between control or BPS-exposed females were eliminated with L-NAME. Increased dilatory responses to ACh after acute BPS exposure were observed in aortic rings from female mice only, and differences were eliminated with inhibition of eNOS or inhibition of ER.Conclusion: Prenatal BPS exposure leads to persistent changes in endothelium-dependent vascular function in a sex-specific manner that appears to be modulated by interaction of BPS with ER signaling. |
| first_indexed | 2024-04-13T19:05:32Z |
| format | Article |
| id | doaj.art-1e6fb1c0a5a64ab397e7fa8fb3959e04 |
| institution | Directory Open Access Journal |
| issn | 2673-3080 |
| language | English |
| last_indexed | 2024-04-13T19:05:32Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Toxicology |
| spelling | doaj.art-1e6fb1c0a5a64ab397e7fa8fb3959e042022-12-22T02:33:58ZengFrontiers Media S.A.Frontiers in Toxicology2673-30802022-10-01410.3389/ftox.2022.933572933572Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspringLiam T. Connors0Liam T. Connors1Liam T. Connors2Hai-Lei Zhu3Hai-Lei Zhu4Manvir Gill5Emma Walsh6Emma Walsh7Radha D. Singh8Radha D. Singh9Radha D. Singh10Radha D. Singh11Sarah Easson12Sarah Easson13Sarah Easson14Sofia B. Ahmed15Sofia B. Ahmed16Hamid R. Habibi17William C. Cole18William C. Cole19William C. Cole20Jennifer A. Thompson21Jennifer A. Thompson22Jennifer A. Thompson23Jennifer A. Thompson24Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaDepartment of Biological Sciences, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaDepartment of Biological Sciences, University of Calgary, Calgary, AB, CanadaDepartment of Physiology and Pharmacology, University of Calgary, Calgary, AB, CanadaLibin Cardiovascular Institute, University of Calgary, Calgary, AB, CanadaAlberta Children’s Hospital Research Institute, University of Calgary, Calgary, AB, CanadaCumming School of Medicine, University of Calgary, Calgary, AB, CanadaBackground: Bisphenol S (BPS) is among the most commonly used substitutes for Bisphenol A (BPA), an endocrine disrupting chemical used as a plasticizer in the manufacture of polycarbonate plastics and epoxy resins. Bisphenols interfere with estrogen receptor (ER) signaling, which modulates vascular function through stimulation of nitric oxide (NO) production via endothelial nitric oxide synthase (eNOS). BPS can cross into the placenta and 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 substitutes, particularly with respect to the vasculature.Objective: To determine if prenatal BPS exposure influences vascular health in adulthood.Methods: At the time of mating, female C57BL/6 dams were administered BPS (250 nM) or vehicle control in the drinking water, and exposure continued during lactation. At 12-week of age, mesenteric arteries were excised from male and female offspring and assessed for responses to an endothelium-dependent (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP) vasodilator. Endothelium-dependent dilation was measured in the presence or absence of L-NAME, an eNOS inhibitor. To further explore the role of NO and ER signaling, wire myography was used to assess ACh responses in aortic rings after acute exposure to BPS in the presence or absence of L-NAME or an ER antagonist.Results: Increased ACh dilation and increased sensitivity to Phe were observed in microvessels from BPS-exposed females, while no changes were observed in male offspring. Differences in ACh-induced dilation between control or BPS-exposed females were eliminated with L-NAME. Increased dilatory responses to ACh after acute BPS exposure were observed in aortic rings from female mice only, and differences were eliminated with inhibition of eNOS or inhibition of ER.Conclusion: Prenatal BPS exposure leads to persistent changes in endothelium-dependent vascular function in a sex-specific manner that appears to be modulated by interaction of BPS with ER signaling.https://www.frontiersin.org/articles/10.3389/ftox.2022.933572/fullEndotheliumnitric oxideestrogendevelopmentmicrovascularbisphenol S (BPS) |
| spellingShingle | Liam T. Connors Liam T. Connors Liam T. Connors Hai-Lei Zhu Hai-Lei Zhu Manvir Gill Emma Walsh Emma Walsh Radha D. Singh Radha D. Singh Radha D. Singh Radha D. Singh Sarah Easson Sarah Easson Sarah Easson Sofia B. Ahmed Sofia B. Ahmed Hamid R. Habibi William C. Cole William C. Cole William C. Cole Jennifer A. Thompson Jennifer A. Thompson Jennifer A. Thompson Jennifer A. Thompson Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring Frontiers in Toxicology Endothelium nitric oxide estrogen development microvascular bisphenol S (BPS) |
| title | Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring |
| title_full | Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring |
| title_fullStr | Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring |
| title_full_unstemmed | Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring |
| title_short | Prenatal exposure to a low dose of BPS causes sex-dependent alterations to vascular endothelial function in adult offspring |
| title_sort | prenatal exposure to a low dose of bps causes sex dependent alterations to vascular endothelial function in adult offspring |
| topic | Endothelium nitric oxide estrogen development microvascular bisphenol S (BPS) |
| url | https://www.frontiersin.org/articles/10.3389/ftox.2022.933572/full |
| work_keys_str_mv | AT liamtconnors prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT liamtconnors prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT liamtconnors prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT haileizhu prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT haileizhu prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT manvirgill prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT emmawalsh prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT emmawalsh prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT radhadsingh prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT radhadsingh prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT radhadsingh prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT radhadsingh prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT saraheasson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT saraheasson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT saraheasson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT sofiabahmed prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT sofiabahmed prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT hamidrhabibi prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT williamccole prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT williamccole prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT williamccole prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT jenniferathompson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT jenniferathompson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT jenniferathompson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring AT jenniferathompson prenatalexposuretoalowdoseofbpscausessexdependentalterationstovascularendothelialfunctioninadultoffspring |