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Research article - Peer-reviewed, 2021

Perfluorooctane sulfonate (PFOS) exposure of bovine oocytes affects early embryonic development at human-relevant levels in an in vitro model

Hallberg, Ida; Persson, Sara; Olovsson, Matts; Sirard, Marc-Andre; Damdimopoulou, Pauliina; Ruegg, Joelle; Sjunnesson, Ylva C. B.;

Abstract

Perfluorooctane sulfonate (PFOS) has been added to Stockholm Convention for global phase out, but will continue to contribute to the chemical burden in humans for a long time to come due to extreme persistence in the environment. In the body, PFOS is transferred into to the ovarian follicular fluid that surrounds the maturing oocyte. In the present study, bovine cumulus oocyte complexes were exposed to PFOS during 22 h in vitro maturation. Concentrations of 2 ng g(-1) (PFOS-02) representing average human exposure and 53 ng g(-1) (PFOS-53) relevant to highly exposed groups were used. After exposure, developmental competence was recorded until day 8 after fertilisation. Blastocysts were fixed and either stained to evaluate blastomere number and lipid distribution using confocal microscopy or frozen and pooled for microarray-based gene expression and DNA methylation analyses.PFOS-53 delayed the first cleavage to two-cell stage and beyond at 44 h after fertilisation (p < .01). No reduction of proportion blastocysts were seen at day 8 in either of the groups, but PFOS-53 exposure resulted in delayed development into more advanced stages of blastocysts seen as both reduced developmental stage (p = .001) and reduced number of blastomeres (p = .04). Blastocysts showed an altered lipid distribution that was more pronounced after exposure to PFOS-53 (increased total lipid volume, p=.0003, lipid volume/cell p < .0001) than PFOS-02, where only decreased average lipid droplet size (p=.02) was observed. Gene expression analyses revealed pathways differently regulated in the PFOS-treated groups compared to the controls, which were related to cell death and survival through e.g., P38 mitogen-activated protein kinases and signal transducer and activator of transcription 3, which in turn activates tumour protein 53 (TP53). Transcriptomic changes were also associated with metabolic stress response, differentiation and proliferation, which could help to explain the phenotypic changes seen in the blastocysts. The gene expression changes were more pronounced after exposure to PFOS-53 compared to PFOS-02. DNA-methylation changes were associated with similar biological functions as the transcriptomic data, with the most significantly associated pathway being TP53. Collectively, these results reveal that brief PFOS exposure during oocyte maturation alters the early embryo development at concentrations relevant to humans. This study adds to the evidence that PFOS has the potential to affect female fertility.

Keywords

Perfluorooctane sulfonate; Bovine in vitro embryo production; Oocyte maturation; Lipid distribution; Gene-expression

Published in

Toxicology

2021, volume: 464, article number: 153028
Publisher: ELSEVIER IRELAND LTD

Authors' information

Swedish University of Agricultural Sciences, Department of Clinical Sciences
Swedish University of Agricultural Sciences, Department of Clinical Sciences
Olovsson, Matts
Uppsala University
Sirard, Marc-Andre
Laval University
Damdimopoulou, Pauliina
Karolinska University Hospital
Ruegg, Joelle
Uppsala University
Swedish University of Agricultural Sciences, Department of Clinical Sciences

Sustainable Development Goals

SDG5 Gender equality
SDG3 Good health and wellbeing

UKÄ Subject classification

Pharmacology and Toxicology

Publication Identifiers

DOI: https://doi.org/10.1016/j.tox.2021.153028

URI (permanent link to this page)

https://res.slu.se/id/publ/114434