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

Hanna Katarina Lilith Johansson, Terje Svingen, Julie Boberg, Paul A Fowler , David Stead, Anne Marie Vinggaard, Panagiotis Filis* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)
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Disruption of sensitive stages of ovary development during fetal and perinatal life can have severe and life-long consequences for a woman’s reproductive life. Exposure to endocrine disrupting chemicals may affect ovarian development, leading to subsequent reproductive disorders. Here, we investigated the effect of early life exposure to defined mixtures of human-relevant endocrine disrupting chemicals on the rat ovary. We aimed to identify molecular events involved in pathogenesis of ovarian dysgenesis syndrome that have potential for future adverse outcome pathway development. We therefore focused on the ovarian proteome. Rats were exposed to a mixture of phthalates, pesticides, UV-filters, bisphenol A, butyl-paraben, and paracetamol during gestation and lactation. The chemicals were tested together or in subgroups of chemicals with anti-androgenic or estrogenic potentials at doses 450-times human exposure. Paracetamol was tested separately, at a dose of 360 mg/kg. Using shotgun proteomics on ovaries from pup day 17 offspring, we observed exposure effects on the proteomes. Nine proteins were affected in more than one exposure group and of these, we conclude that calretinin is a potential key event biomarker of early endocrine disruption in the ovary.
Original languageEnglish
Pages (from-to)1241-1250
Number of pages10
JournalArchives of Toxicology
Early online date27 Mar 2020
Publication statusPublished - Apr 2020

Bibliographical note

Open Access via Springer Compact
This work was funded by the Ministry of Environment and Food of Denmark, and by a grant from the European Commission 7th Framework Program CONTAMED (Contaminant mixtures and human reproductive health-novel strategies for health impact and risk assessment of endocrine disrupters, grant agreement no.: 215202), as well as the Medical Research Council (UK) (MR/L010011/1 to PAF) and the EU Horizon 2020 project FREIA (Grant Number 825100). We would like to thank Heidi Letting, the Animal facilities at DTU food, and the University of Aberdeen Proteomics Core Facility for their support and assistance in this work.


  • ovary
  • proteome
  • endocrine disruptor
  • calretinin
  • Ovarian Dysgenesis Syndrome
  • AOP
  • Calretinin
  • Ovarian dysgenesis syndrome
  • Endocrine disruption
  • Proteome
  • Ovary
  • AGE


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