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Identification of p...
Identification of phthalate mixture exposure targets in the human and mouse ovary in vitro
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- Tarvainen, Ilari (author)
- Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gynecol & Reprod Med, Stockholm, Sweden.
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- Soto, Delia A. (author)
- Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Laws, Mary J. (author)
- Univ Illinois, Dept Comparat Biosci, Champaign, IL USA.
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- Duque Björvang, Richelle (author)
- Uppsala universitet,Obstetrisk och reproduktiv hälsoforskning,Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Damdimopoulos, Anastasios (author)
- Karolinska Institutet
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- Roos, Kristine (author)
- Tallinn Univ Technol, Dept Chem & Biotechnol, Tallinn, Estonia.;Nova Vita Clin, Tallinn, Estonia.
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- Li, Tianyi (author)
- Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gynecol & Reprod Med, Stockholm, Sweden.
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- Kramer, Stav (author)
- Univ Illinois, Dept Comparat Biosci, Champaign, IL USA.
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- Li, Zhong (author)
- Univ Illinois, Roy J Carver Biotechnol Ctr, Champaign, IL USA.
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- Lavogina, Darja (author)
- Competence Ctr Hlth Technol, Tartu, Estonia.;Univ Tartu, Inst Chem, Tartu, Estonia.
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- Visser, Nadja (author)
- Uppsala universitet,Reproduktionsbiologi
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- Kunovac Kallak, Theodora, 1985- (author)
- Uppsala universitet,Reproduktiv hälsa
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- Lager, Susanne (author)
- Uppsala universitet,Obstetrisk och reproduktiv hälsoforskning
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- Gidlöf, Sebastian (author)
- Karolinska Institutet
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- Edlund, Erik (author)
- Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gynecol & Reprod Med, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
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- Papaikonomou, Kiriaki (author)
- Karolinska Institutet
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- Öberg, Mattias (author)
- Karolinska Inst, Inst Environm Med, Unit Integrat Toxicol, Stockholm, Sweden.
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- Olovsson, Matts, 1958- (author)
- Uppsala universitet,Reproduktionsbiologi
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- Salumets, Andres (author)
- Karolinska Institutet
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- Velthut-Meikas, Agne (author)
- Tallinn Univ Technol, Dept Chem & Biotechnol, Tallinn, Estonia.
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- Flaws, Jodi A. (author)
- Karolinska Univ Hosp, Stockholm, Sweden.;Univ Illinois, Dept Comparat Biosci, Champaign, IL USA.
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- Damdimopoulou, Pauliina (author)
- Karolinska Institutet
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Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gynecol & Reprod Med, Stockholm, Sweden. Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (creator_code:org_t)
- Elsevier, 2023
- 2023
- English.
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In: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 119
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Abstract
Subject headings
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- Chemical health risk assessment is based on single chemicals, but humans and wildlife are exposed to extensive mixtures of industrial substances and pharmaceuticals. Such exposures are life-long and correlate with multiple morbidities, including infertility. How combinatorial effects of chemicals should be handled in hazard charac-terization and risk assessment are open questions. Further, test systems are missing for several relevant health outcomes including reproductive health and fertility in women. Here, our aim was to screen multiple ovarian cell models for phthalate induced effects to identify biomarkers of exposure. We used an epidemiological cohort study to define different phthalate mixtures for in vitro testing. The mixtures were then tested in five cell models representing ovarian granulosa or stromal cells, namely COV434, KGN, primary human granulosa cells, primary mouse granulosa cells, and primary human ovarian stromal cells. Exposures at epidemiologically relevant levels did not markedly elicit cytotoxicity or affect steroidogenesis in short 24-hour exposure. However, significant effects on gene expression were identified by RNA-sequencing. Altogether, the exposures changed the expression of 124 genes on the average (9-479 genes per exposure) in human cell models, without obvious concentration or mixture-dependent effects on gene numbers. The mixtures stimulated distinct changes in different cell models. Despite differences, our analyses suggest commonalities in responses towards phthalates, which forms a starting point for follow-up studies on identification and validation of candidate biomarkers that could be developed to novel assays for regulatory testing or even into clinical tests.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- Phthalates
- Endocrine disrupting chemicals
- Chemical mixtures
- Reproduction
- Ovaries
- Female fertility
- Risk assessment
- In vitro models
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Tarvainen, Ilari
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Soto, Delia A.
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Laws, Mary J.
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Duque Björvang, ...
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Damdimopoulos, A ...
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Roos, Kristine
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Li, Tianyi
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Kramer, Stav
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Li, Zhong
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Lavogina, Darja
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Visser, Nadja
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Kunovac Kallak, ...
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Lager, Susanne
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Gidlöf, Sebastia ...
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Edlund, Erik
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Papaikonomou, Ki ...
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Öberg, Mattias
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Olovsson, Matts, ...
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Salumets, Andres
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Velthut-Meikas, ...
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Flaws, Jodi A.
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Damdimopoulou, P ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Obstetrics Gynae ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmacology and ...
- Articles in the publication
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Reproductive Tox ...
- By the university
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Uppsala University
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Karolinska Institutet