Female Reproductive toxicity of EDCs: a human evidence-based screening and Identification Approach

Project Information

FREIA

Grant agreement ID: 825100

DOI 10.3030/825100

Project closed

EC signature date 3 December 2018

Start date 1 January 2019

End date 30 June 2024

Funded under

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Total cost € 6 104 476,25

EU contribution € 6 104 476,25

Coordinated by

STICHTING VU
Netherlands

Deliverables

Websites, patent fillings, videos etc. (3)

EDC Testing Conference

End-of-project conference, to be organised with EDC testing cluster, to present advances in EDC testing (strategies) resulting from the SC1-BHC-27-2018 call, including FREIA’s outcomes, to relevant stakeholders and disseminate FREIA test strategy and test methodologies.

Public Website online

FREIA public WEB portal with description of the project, challenges and goals, project members and updates on current activities (including news/conferences/workshops).

Collaborative website (intranet) ready to use

Platform for secured internal information exchange and project documents archive.

Documents, reports (2)

Health promotion Strategy

Health Promotion Strategy based on collated information gathered and generated on EDCs and effects on female reproductive health, to be used for promotion of female reproductive health.

FREIA stakeholder database (updated continuously)

Database of relevant actors and stakeholder groups for dissemination, communication and exploitation purposes.

Publications

Peer reviewed articles (35)

The mammalian ovary: Concerns about the evaluation of prenatal environmental exposures

Author(s): Laetitia L. Lecante; Pauline Lelandais; Séverine Mazaud-Guittot; Paul A. Fowler
Published in: Current Opinion in Endocrine and Metabolic Research, Issue 18, 2021, Page(s) 171–177, ISSN 2451-9650
Publisher: Elsevier Ltd.
DOI: 10.1016/j.coemr.2021.03.012

Bovine In Vitro Oocyte Maturation and Embryo Production Used as a Model for Testing Endocrine Disrupting Chemicals Eliciting Female Reproductive Toxicity With Diethylstilbestrol as a Showcase Compound

Author(s): Asimaki, K; Vazakidou, P; van Tol, H T A; Oei, C H Y; Modder, E A; van Duursen, M B M; Gadella, B M; dES/dFAH FR; FAH klinische reproductie; Veterinaire biochemie; dB&C FR-RMSC FR
Published in: Frontiers in Toxicology, Issue 2, 4, 2022, ISSN 2673-3080
Publisher: Frontiers
DOI: 10.3389/ftox.2022.811285

Six Decades of Research on Human Fetal Gonadal Steroids

Author(s): Stéphane Connan-Perrot, Thibaut Léger, Pauline Lelandais, Christèle Desdoits-Lethimonier, Arthur David, Paul A. Fowler, Séverine Mazaud-Guittot
Published in: International Journal of Molecular Sciences, Issue 22/13, 2021, Page(s) 6681, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms22136681

The profile of steroid hormones in human fetal and adult ovaries.

Author(s): Vazakidou P, Evangelista S, Li T, et al.   . Published 2024 May 22.
Published in: Reprod Biol Endocrinol., Issue 22(1), 2024, Page(s) 60, ISSN 1477-7827
Publisher: BioMed Central
DOI: 10.1186/s12958-024-01233-7

Associations between lifestyle factors and levels of per- and polyfluoroalkyl substances (PFASs), phthalates and parabens in follicular fluid in women undergoing fertility treatment.Epub 2023 Jul 22.

Author(s): Hallberg I, Björvang RD, Hadziosmanovic N, Koekkoekk J, Pikki A, van Duursen M, Lenters V, Sjunnesson Y, Holte J, Berglund L, Persson S, Olovsson M, Damdimopoulou P.
Published in: J Expo Sci Environ Epidemiol., Issue Sep;33(5), 2023, Page(s) 699-709, ISSN 1559-0631
Publisher: Nature Publishing Group
DOI: 10.1038/s41370-023-00579-1

AOP key event relationship report: Linking decreased androgen receptor activation with decreased granulosa cell proliferation of gonadotropin-independent follicles.

Author(s): Panagiotou EM, Draskau MK, Li T, Hirschberg A, Svingen T, Damdimopoulou P. :. doi: 10.1016/j.reprotox.2022.07.004. Epub 2022 Jul 19. PMID: 35868514.
Published in: Reproductive Toxicology, Issue Sep;112, 2022, Page(s) 136-147, ISSN 0890-6238
Publisher: Elsevier BV
DOI: 10.1016/j.reprotox.2022.07.004

Exposure to the pesticides linuron, dimethomorph and imazalil alters steroid hormone profiles and gene expression in developing rat ovaries.

Author(s): Boberg J, Johansson HKL, Franssen D, et al.
Published in: Toxicol Lett., Issue 373, 2023, Page(s) 114-122, ISSN 0378-4274
Publisher: Elsevier BV
DOI: 10.1016/j.toxlet.2022.11.010

Persistent organic pollutants dysregulate energy homeostasis in human ovaries in vitro

Author(s): Tianyi Li, Richelle D. Björvang, Jie Hao, Valentina Di Nisio, Anastasios Damdimopoulos, Cecilia Lindskog, Kiriaki Papaikonomou, Pauliina Damdimopoulou
Published in: Environment International, Issue 187, 2024, Page(s) 108710, ISSN 0160-4120
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2024.108710

Maternal exposure to ambient black carbon particles and their presence in maternal and fetal circulation and organs: an analysis of two independent population-based observational studies

Author(s): Eva Bongaerts, Laetitia L Lecante, Hannelore Bové, Maarten B J Roeffaers, Marcel Ameloot, Paul A Fowler, Tim S Nawrot
Published in: The Lancet Planetary Health, Issue 6, 2024, Page(s) e804-e811, ISSN 2542-5196
Publisher: Elsevier
DOI: 10.1016/s2542-5196(22)00200-5

Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models

Author(s): Tianyi Li 1, Paraskevi Vazakidou 2, Pim E G Leonards 3, Anastasios Damdimopoulos 4, Eleftheria Maria Panagiotou 5, Catarina Arnelo 6, Kerstin Jansson 7, Karin Pettersson 8, Kiriaki Papaikonomou 9, Majorie van Duursen 10, Pauliina Damdimopoulou 11
Published in: Toxicology, Issue 485, 2023, Page(s) 153425, ISSN 0300-483X
Publisher: Elsevier BV
DOI: 10.1016/j.tox.2023.153425

High throughput LC-MS/MS method for steroid hormone analysis in rat liver and plasma - unraveling methodological challenges.

Author(s): Evangelista S, Vazakidou P, Koekkoek J, Heinzelmann MT, Lichtensteiger W, Schlumpf M, Tresguerres JAF, Linillos-Pradillo B, van Duursen MBM, Lamoree MH, Leonards PEG
Published in: Talanta, Issue Jul 24, 2023, Page(s) 266(Pt 1):124981, ISSN 0039-9140
Publisher: Elsevier BV
DOI: 10.1016/j.talanta.2023.124981

In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity.

Author(s): Rooda, I., Hassan, J., Hao, J. et al.
Published in: Nat Commun, Issue 15, 6989, 2024, ISSN 0890-6238
Publisher: Elsevier BV
DOI: 10.1038/s41467-024-51185-0

Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies

Author(s): Richelle D. Björvang; Ida Hallberg; Anne Pikki; Lars Berglund; Matteo Pedrelli; Hannu Kiviranta; Panu Rantakokko; Päivi Ruokojärvi; Christian H. Lindh; Matts Olovsson; Sara Persson; Jan Holte; Ylva Sjunnesson; Pauliina Damdimopoulou
Published in: Environmental Research, Issue 208, 2021, Page(s) 112626, ISSN 0013-9351
Publisher: Academic Press
DOI: 10.1016/j.envres.2021.112626

Quantitative analysis of ovarian surface photographs as a tool for assessment of chemical effects on folliculogenesis and ovulation in rats

Author(s): Tianyi Li, Julie Boberg, Hanna K L Johansson, Valentina Di Nisio, Sofie Christiansen, Terje Svingen, Pauliina Damdimopoulou
Published in: Reproductive Toxicology, Issue Aug;119, 2023, Page(s) 108416, ISSN 0890-6238
Publisher: Elsevier BV
DOI: 10.1016/j.reprotox.2023.108416

Effects of chemical in vitro activation versus fragmentation on human ovarian tissue and follicle growth in culture.

Author(s): Hao J, Li T, Heinzelmann M, et al.
Published in: Hum Reprod Open., Issue (3), 2024, Page(s) hoae028 Published 2024 May 22, ISSN 2399-3529
Publisher: Oxford University Press
DOI: 10.1093/hropen/hoae028

The insulin-like growth factor system: A target for endocrine disruptors?

Author(s): Chiara Talia, Lisa Connolly, Paul A. Fowler
Published in: Environment International, Issue Volume 147, February 2021, 106311, 2021, Page(s) 106311, ISSN 0160-4120
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2020.106311

From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures.

Author(s): Caporale N, Leemans M, Birgersson L, et al.
Published in: Science, Issue 375(6582), 2022, Page(s) eabe8244, ISSN 1095-9203
Publisher: Washington, D.C.
DOI: 10.1126/science.abe8244

Association between chemical mixtures and female fertility in women undergoing assisted reproduction in Sweden and Estonia

Author(s): Andrea Bellavia 1, Runyu Zou 2, Richelle D Björvang 3, Kristine Roos 4, Ylva Sjunnesson 5, Ida Hallberg 5, Jan Holte 6, Anne Pikki 6, Virissa Lenters 7, Lützen Portengen 8, Jacco Koekkoek 9, Marja Lamoree 9, Majorie Van Duursen 9, Roel Vermeulen 2, Andres Salumets 10, Agne Velthut-Meikas 11, Pauliina Damdimopoulou 3
Published in: Environ Res, Issue 216(Pt 1), 2023, Page(s) 114447, ISSN 0013-9351
Publisher: Academic Press
DOI: 10.1016/j.envres.2022.114447

A putative adverse outcome pathway network for disrupted female pubertal onset to improve testing and regulation of endocrine disrupting chemicals

Author(s): Delphine Franssen, Terje Svingen, David Lopez Rodriguez, Majorie Van Duursen, Julie Boberg, Anne-Simone Parent
Published in: Neuroendocrinology, 2021, ISSN 0028-3835
Publisher: S. Karger AG
DOI: 10.1159/000515478

Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells

Author(s): Magdalena Wagner, Masahito Yoshihara, Iyadh Douagi, Anastasios Damdimopoulos, Sarita Panula, Sophie Petropoulos, Haojiang Lu, Karin Pettersson, Kerstin Palm, Shintaro Katayama, Outi Hovatta, Juha Kere, Fredrik Lanner, Pauliina Damdimopoulou
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-14936-3

Persistent environmental endocrine-disrupting chemicals in ovarian follicular fluid and in vitro fertilization treatment outcome in women

Author(s): Richelle D. Björvang, Pauliina Damdimopoulou
Published in: Upsala Journal of Medical Sciences, Issue 125/2, 2020, Page(s) 85-94, ISSN 0300-9734
Publisher: Taylor & Francis
DOI: 10.1080/03009734.2020.1727073

Safeguarding Female Reproductive Health Against Endocrine Disrupting Chemicals—The FREIA Project

Author(s): Majorie B. M. van Duursen, Julie Boberg, Sofie Christiansen, Lisa Connolly, Pauliina Damdimopoulou, Panagiotis Filis, Paul A. Fowler, Bart M. Gadella, Jan Holte, Kersti Jääger, Hanna K. L. Johansson, Tianyi Li, Séverine Mazaud-Guittot, Anne-Simone Parent, Andres Salumets, Ana M. Soto, Terje Svingen, Agne Velthut-Meikas, Eva Bay Wedebye, Yuling Xie, Martin van den Berg
Published in: International Journal of Molecular Sciences, Issue 21/9, 2020, Page(s) 3215, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms21093215

Dynamics of the transcriptional landscape during human fetal testis and ovary development

Author(s): Estelle Lecluze, Antoine D Rolland, Panagiotis Filis, Bertrand Evrard, Sabrina Leverrier-Penna, Millissia Ben Maamar, Isabelle Coiffec, Vincent Lavoué, Paul A Fowler, Séverine Mazaud-Guittot, Bernard Jégou, Frédéric Chalmel
Published in: Human Reproduction, Issue 35/5, 2020, Page(s) 1099-1119, ISSN 0268-1161
Publisher: Oxford University Press
DOI: 10.1093/humrep/deaa041

Testing the twin testosterone transfer hypothesis—intergenerational analysis of 317 dizygotic twins born in Aberdeen, Scotland

Author(s): Chiara Talia, Edwin-Amalraj Raja, Sohinee Bhattacharya, Paul A Fowler
Published in: Human Reproduction, 2020, ISSN 0268-1161
Publisher: Oxford University Press
DOI: 10.1093/humrep/deaa091

Calretinin is a novel candidate marker for adverse ovarian effects of early life exposure to mixtures of endocrine disruptors in the rat

Author(s): Hanna Katarina Lilith Johansson, Terje Svingen, Julie Boberg, Paul A. Fowler, David Stead, Anne Marie Vinggaard, Panagiotis Filis
Published in: Archives of Toxicology, Issue 94/4, 2020, Page(s) 1241-1250, ISSN 0340-5761
Publisher: Springer Verlag
DOI: 10.1007/s00204-020-02697-3

Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals

Author(s): Hanna K. L. Johansson, Pauliina Damdimopoulou, Majorie B. M. van Duursen, Julie Boberg, Delphine Franssen, Marijke de Cock, Kersti Jääger, Magdalena Wagner, Agne Velthut-Meikas, Yuling Xie, Lisa Connolly, Pauline Lelandais, Severine Mazaud-Guittot, Andres Salumets, Monica Kam Draskau, Panagiotis Filis, Paul A. Fowler, Sofie Christiansen, Anne-Simone Parent, Terje Svingen
Published in: Archives of Toxicology, 2020, ISSN 0340-5761
Publisher: Springer Verlag
DOI: 10.1007/s00204-020-02834-y

Classical toxicity endpoints in female rats are insensitive to the human endocrine disruptors diethylstilbestrol and ketoconazole

Author(s): Hanna K.L. Johansson, Sofie Christiansen, Monica Kam Draskau, Terje Svingen, Julie Boberg
Published in: Reproductive Toxicology, Issue 101, 2021, Page(s) 9-17, ISSN 0890-6238
Publisher: Elsevier BV
DOI: 10.1016/j.reprotox.2021.01.003

Acetaminophen (APAP, Paracetamol) Interferes With the First Trimester Human Fetal Ovary Development in an Ex Vivo Model.

Author(s): Lecante LL, Leverrier-Penna S, Gicquel T, et al.
Published in: J Clin Endocrinol Metab., Issue 107(6), 2022, Page(s) 1647-1661, ISSN 1945-7197
Publisher: Oxford University Press
DOI: 10.1210/clinem/dgac080

Comparison of female rat reproductive effects of pubertal versus adult exposure to known endocrine disruptors.

Author(s): Julie Boberg1 Tianyi Li2,3 Sofie Christiansen1 Monica K. Draskau1 Pauliina Damdimopoulou2,3 Terje Svingen1 Hanna K. L. Johansson1*
Published in: Frontiers in Endocrinology, Issue 14, 2023, ISSN 1124-1292
Publisher: Frontiers Media
DOI: 10.3389/fendo.2023.1126485

A Pragmatic Approach to Adverse Outcome Pathway Development and Evaluation

Author(s): Terje Svingen, Daniel L Villeneuve, Dries Knapen, Eleftheria Maria Panagiotou, Monica Kam Draskau, Pauliina Damdimopoulou, Jason M O’Brien
Published in: Toxicological Sciences, Issue 184, 2021, Page(s) 183-190, ISSN 1096-6080
Publisher: Oxford University Press
DOI: 10.1093/toxsci/kfab113

Perinatal exposure to the fungicide ketoconazole alters hypothalamic control of puberty in female rats.

Author(s): Franssen D, Johansson HKL, Lopez-Rodriguez D, Lavergne A, Terwagne Q, Boberg J, Christiansen S, Svingen T, Parent A-S
Published in: Front Endocrinol, Issue Apr 3;14, 2023, Page(s) 1140886, ISSN 1664-2392
Publisher: Frontiers Media SA
DOI: 10.3389/fendo.2023.1140886

A method for in vitro data and structure curation to optimize for QSAR modelling of minimum absolute potency levels and a comparative use case.

Author(s): Nikolov NG, Nissen ACVE, Wedebye EB.
Published in: Environ Toxicol Pharmacol., Issue Mar;98, 2023, Page(s) 104069, ISSN 1382-6689
Publisher: Elsevier BV
DOI: 10.1016/j.etap.2023.104069

Transcriptional profiling of the developing rat ovary following intrauterine exposure to the endocrine disruptors diethylstilbestrol and ketoconazole

Author(s): Indusha Kugathas; Hanna K. L. Johansson; Edith Chan Sock Peng; Maryne Toupin; Bertrand Evrard; Thomas A. Darde; Julie Boberg; Monica K. Draskau; Antoine D. Rolland; Séverine Mazaud-Guittot; Frédéric Chalmel; Terje Svingen
Published in: Crossref, Issue 5, 2023, Page(s) 849–863, ISSN 0340-5761
Publisher: Springer Verlag
DOI: 10.1007/s00204-023-03442-2

Ketoconazole blocks progesterone production without affecting other parameters of cumulus-oocyte complex maturation

Author(s): K. Asimaki, P. Vazakidou, H.T.A. van Tol, M.B.M. van Duursen, B.M. Gadella
Published in: Reproductive Toxicology, Issue 128, 2024, Page(s) 108637, ISSN 0890-6238
Publisher: Elsevier BV
DOI: 10.1016/j.reprotox.2024.108637

Best practices to quantify the impact of reproductive toxicants on development, function, and diseases of the rodent mammary gland.

Author(s): Matouskova K, Szabo GK, Daum J, Fenton SE, Christiansen S, Soto AM, Kay JE, Cardona B, Vandenberg LN.
Published in: Reproductive Toxicology, Issue Sep;112, 2022, Page(s) 51-67, ISSN 0890-6238
Publisher: Elsevier BV
DOI: 10.1016/j.reprotox.2022.06.011

Non-peer reviewed articles (2)

Maternal over-the-counter analgesics use during pregnancy and adverse perinatal outcomes: Cohort study of 151,141 singleton pregnancies

Author(s): Zafeiri A, Raja EA, Mitchell RT, Hay DC, Bhattacharya S, Fowler PA.
Published in: BMJ Open, Issue 2022 May 3, 2022, Page(s) 12(5):e048092, ISSN 2044-6055
Publisher: BMJ Publishing Group
DOI: 10.1136/bmjopen-2020-048092

Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities

Author(s): Kay JE, Cardona B, Rudel RA, Vandenberg LN, Soto AM, Christiansen S, Birnbaum LS, Fenton SE.
Published in: Curr Environ Health Rep, Issue Dec;9(4), 2022, Page(s) 535-562, ISSN 2196-5412
Publisher: Springer International Publishing AG
DOI: 10.1007/s40572-022-00376-2