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  • Tarvainen, IlariKarolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gynecol & Reprod Med, Stockholm, Sweden. (author)

Identification of phthalate mixture exposure targets in the human and mouse ovary in vitro

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-507546
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-507546URI
  • https://doi.org/10.1016/j.reprotox.2023.108393DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:152894451URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Soto, Delia A.Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (author)
  • Laws, Mary J.Univ Illinois, Dept Comparat Biosci, Champaign, IL USA. (author)
  • Duque Björvang, RichelleUppsala universitet,Obstetrisk och reproduktiv hälsoforskning,Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.(Swepub:uu)ricdu778 (author)
  • Damdimopoulos, AnastasiosKarolinska Institutet (author)
  • Roos, KristineTallinn Univ Technol, Dept Chem & Biotechnol, Tallinn, Estonia.;Nova Vita Clin, Tallinn, Estonia. (author)
  • Li, TianyiKarolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Gynecol & Reprod Med, Stockholm, Sweden. (author)
  • Kramer, StavUniv Illinois, Dept Comparat Biosci, Champaign, IL USA. (author)
  • Li, ZhongUniv Illinois, Roy J Carver Biotechnol Ctr, Champaign, IL USA. (author)
  • Lavogina, DarjaCompetence Ctr Hlth Technol, Tartu, Estonia.;Univ Tartu, Inst Chem, Tartu, Estonia. (author)
  • Visser, NadjaUppsala universitet,Reproduktionsbiologi(Swepub:uu)nadvi208 (author)
  • Kunovac Kallak, Theodora,1985-Uppsala universitet,Reproduktiv hälsa(Swepub:uu)theka349 (author)
  • Lager, SusanneUppsala universitet,Obstetrisk och reproduktiv hälsoforskning(Swepub:uu)susla462 (author)
  • Gidlöf, SebastianKarolinska Institutet (author)
  • Edlund, ErikKarolinska 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. (author)
  • Papaikonomou, KiriakiKarolinska Institutet (author)
  • Öberg, MattiasKarolinska Inst, Inst Environm Med, Unit Integrat Toxicol, Stockholm, Sweden. (author)
  • Olovsson, Matts,1958-Uppsala universitet,Reproduktionsbiologi(Swepub:uu)mattolov (author)
  • Salumets, AndresKarolinska Institutet (author)
  • Velthut-Meikas, AgneTallinn Univ Technol, Dept Chem & Biotechnol, Tallinn, Estonia. (author)
  • Flaws, Jodi A.Karolinska Univ Hosp, Stockholm, Sweden.;Univ Illinois, Dept Comparat Biosci, Champaign, IL USA. (author)
  • Damdimopoulou, PauliinaKarolinska Institutet (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 Clin Sci, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden. (creator_code:org_t)

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  • In:Reproductive Toxicology: Elsevier1190890-62381873-1708

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