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

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Abstract

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
Volume94
Early online date27 Mar 2020
DOIs
Publication statusPublished - Apr 2020

Keywords

  • ovary
  • proteome
  • endocrine disruptor
  • calretinin
  • Ovarian Dysgenesis Syndrome
  • AOP
  • Calretinin
  • Ovarian dysgenesis syndrome
  • Endocrine disruption
  • Proteome
  • FEMALE
  • Ovary
  • CHEMICALS
  • INTRAUTERINE
  • OUTCOME PATHWAYS
  • MENOPAUSE
  • EXPRESSION
  • PROTEOMICS
  • AGE

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  • Equipment

    Aberdeen Proteomics

    David Stead (Manager)

    Medical Sciences

    Research Facilities: Facility

  • Iain Fraser Cytometry Centre

    Andrea Holme (Manager), Linda Duncan (Senior Application Scientist), Ailsa Laird (Technician) & Kate Burgoyne (Technician)

    Institute of Medical Sciences

    Research Facilities: Facility

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