Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models
Due to its sensitivity to hormonal signaling, the mammary gland is often referred to as a sentinel organ for the study of endocrine-disrupting chemicals (EDCs), environmental pollutants that can interfere with the estrogen signaling pathway and induce mammary developmental defects. If and how EDCs i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Environment International |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412023004051 |
| _version_ | 1827816200043757568 |
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| author | Aurélie Lacouture Yann Breton Cindy Weidmann Sarah-Maude Goulet Lucas Germain Martin Pelletier Étienne Audet-Walsh |
| author_facet | Aurélie Lacouture Yann Breton Cindy Weidmann Sarah-Maude Goulet Lucas Germain Martin Pelletier Étienne Audet-Walsh |
| author_sort | Aurélie Lacouture |
| collection | DOAJ |
| description | Due to its sensitivity to hormonal signaling, the mammary gland is often referred to as a sentinel organ for the study of endocrine-disrupting chemicals (EDCs), environmental pollutants that can interfere with the estrogen signaling pathway and induce mammary developmental defects. If and how EDCs impact mammary epithelial cell metabolism has not yet been documented. Herein, to study how estrogens and EDCs modulate mammary gland metabolism, we performed bioenergetic flux analyses using mouse mammary epithelial organoids compared to cells grown in monolayer culture. Several EDCs were tested, including bisphenol A (BPA), its close derivative BPS, a new BPA replacement copolyester called TritanTM, and the herbicide glyphosate. We report that estrogens reprogrammed mammary epithelial cell metabolism differently when grown in two- and three-dimensional models. Specific EDCs were also demonstrated to alter bioenergetic fluxes, thus identifying a new potential adverse effect of these molecules. Notably, organoids were more sensitive to low EDC concentrations, highlighting them as a key model for screening the impact of various environmental pollutants. Mechanistically, transcriptomic analyses revealed that EDCs interfered with the regulation of estrogen target genes and the expression of metabolic genes in organoids. Furthermore, co-treatment with the anti-estrogen fulvestrant blocked these metabolic impacts of EDCs, suggesting that, at least partially, they act through modulation of the estrogen receptor activity. Finally, we demonstrate that mammary organoids can be used for long-term studies on EDC exposure to study alterations in organogenesis/morphogenesis and that past pregnancies can modulate the sensitivity of mammary epithelial organoids to specific EDCs. Overall, this study demonstrates that estrogens and EDCs modulate mammary epithelial cell metabolism in monolayer and organoid cultures. A better understanding of the metabolic impacts of EDCs will allow a better appreciation of their adverse effects on mammary gland development and function. |
| first_indexed | 2024-03-12T00:11:27Z |
| format | Article |
| id | doaj.art-c6e49e9da0ff4b198fa3d6f11128e9e9 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-03-12T00:11:27Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-c6e49e9da0ff4b198fa3d6f11128e9e92023-09-16T05:28:40ZengElsevierEnvironment International0160-41202023-09-01179108132Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional modelsAurélie Lacouture0Yann Breton1Cindy Weidmann2Sarah-Maude Goulet3Lucas Germain4Martin Pelletier5Étienne Audet-Walsh6Endocrinology - Nephrology Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec City, Canada; Intersectoral Centre for Endocrine Disruptor Analysis (CIAPE-ICEDA), Québec City, CanadaInfectious and Immune Diseases Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; ARThrite Research Center, Université Laval, Québec City, CanadaEndocrinology - Nephrology Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec City, CanadaInfectious and Immune Diseases Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; ARThrite Research Center, Université Laval, Québec City, CanadaEndocrinology - Nephrology Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec City, CanadaIntersectoral Centre for Endocrine Disruptor Analysis (CIAPE-ICEDA), Québec City, Canada; Infectious and Immune Diseases Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; ARThrite Research Center, Université Laval, Québec City, Canada; Department of Microbiology-Infectious Diseases and Immunology, Faculty of Medicine, Université Laval, Québec City, Canada; Corresponding authors at: Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada.Endocrinology - Nephrology Research Axis, Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, Canada; Centre de recherche sur le cancer de l’Université Laval, Québec City, Canada; Intersectoral Centre for Endocrine Disruptor Analysis (CIAPE-ICEDA), Québec City, Canada; Corresponding authors at: Centre de recherche du CHU de Québec - Université Laval, Québec City, Canada.Due to its sensitivity to hormonal signaling, the mammary gland is often referred to as a sentinel organ for the study of endocrine-disrupting chemicals (EDCs), environmental pollutants that can interfere with the estrogen signaling pathway and induce mammary developmental defects. If and how EDCs impact mammary epithelial cell metabolism has not yet been documented. Herein, to study how estrogens and EDCs modulate mammary gland metabolism, we performed bioenergetic flux analyses using mouse mammary epithelial organoids compared to cells grown in monolayer culture. Several EDCs were tested, including bisphenol A (BPA), its close derivative BPS, a new BPA replacement copolyester called TritanTM, and the herbicide glyphosate. We report that estrogens reprogrammed mammary epithelial cell metabolism differently when grown in two- and three-dimensional models. Specific EDCs were also demonstrated to alter bioenergetic fluxes, thus identifying a new potential adverse effect of these molecules. Notably, organoids were more sensitive to low EDC concentrations, highlighting them as a key model for screening the impact of various environmental pollutants. Mechanistically, transcriptomic analyses revealed that EDCs interfered with the regulation of estrogen target genes and the expression of metabolic genes in organoids. Furthermore, co-treatment with the anti-estrogen fulvestrant blocked these metabolic impacts of EDCs, suggesting that, at least partially, they act through modulation of the estrogen receptor activity. Finally, we demonstrate that mammary organoids can be used for long-term studies on EDC exposure to study alterations in organogenesis/morphogenesis and that past pregnancies can modulate the sensitivity of mammary epithelial organoids to specific EDCs. Overall, this study demonstrates that estrogens and EDCs modulate mammary epithelial cell metabolism in monolayer and organoid cultures. A better understanding of the metabolic impacts of EDCs will allow a better appreciation of their adverse effects on mammary gland development and function.http://www.sciencedirect.com/science/article/pii/S0160412023004051Endocrine disruptorsOrganoidsBreastBisphenolsTritanGlyphosate |
| spellingShingle | Aurélie Lacouture Yann Breton Cindy Weidmann Sarah-Maude Goulet Lucas Germain Martin Pelletier Étienne Audet-Walsh Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models Environment International Endocrine disruptors Organoids Breast Bisphenols Tritan Glyphosate |
| title | Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models |
| title_full | Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models |
| title_fullStr | Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models |
| title_full_unstemmed | Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models |
| title_short | Estrogens and endocrine-disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two- and three-dimensional models |
| title_sort | estrogens and endocrine disrupting chemicals differentially impact the bioenergetic fluxes of mammary epithelial cells in two and three dimensional models |
| topic | Endocrine disruptors Organoids Breast Bisphenols Tritan Glyphosate |
| url | http://www.sciencedirect.com/science/article/pii/S0160412023004051 |
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