Bovine oocyte exposure to perfluorohexane sulfonate (PFHxS) induces phenotypic, transcriptomic, and DNA methylation changes in resulting embryos in vitro

By Ida Hallberg, Sara Persson, Matts Olovsson, Mikaela Moberg, Petter Ranefall, Denise Laskowski, Pauliina Damdimopoulou, Marc-Andre Sirard, Joëlle Rüegg, and Ylva Sjunnesson
Reproductive Toxicology
March 15, 2022
DOI: 10.1016/j.reprotox.2022.02.004

Knowledge on the effects of perfluorohexane sulfonate (PFHxS) on ovarian function is limited. In the current study, we investigated the sensitivity of oocytes to PFHxS during in vitro maturation (IVM), including consequences on embryo development at the morphological, transcriptomic, and epigenomic levels. Bovine cumulus-oocyte complexes (COCs) were exposed to PFHxS during 22 h IVM. Following fertilisation, developmental competence was recorded until day 8 of culture. Two experiments were conducted: 1) exposure of COCs to 0.01 µg mL^-1 − 100 µg mL^-1 PFHxS followed by confocal imaging to detect neutral lipids and nuclei, and 2) exposure of COCs to 0.1 µg mL^-1 PFHxS followed by analysis of transcriptomic and DNA methylation changes in blastocysts. Decreased oocyte developmental competence was observed upon exposure to ≥ 40 µg mL^-1 PFHxS and altered lipid distribution was observed in the blastocysts upon exposure to 1–10 µg mL^-1 PFHxS (not observed at lower or higher concentrations). Transcriptomic data showed that genes affected by 0.1 µg mL^-1 PFHxS were enriched for pathways related to increased synthesis and production of reactive oxygen species. Enrichment for peroxisome proliferator-activated receptor-γ and oestrogen pathways was also observed. Genes linked to DNA methylation changes were enriched for similar pathways. In conclusion, exposure of the bovine oocyte to PFHxS during the narrow window of IVM affected subsequent embryonic development, as reflected by morphological and molecular changes. This suggests that PFHxS interferes with the final nuclear and cytoplasmic maturation of the oocyte leading to decreased developmental competence to blastocyst stage.

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