Induction of apoptosis in the gonads of Mytilus edulis by metformin and increased temperature, via regulation of HSP70, CASP8, BCL2 and FAS

Wulan Koagouw, Richard J. Hazell, Corina Ciocan

Research output: Contribution to journalArticlepeer-review

Abstract

Pharmaceutically active compounds have been considered contaminants of emerging concern, in response to evidence that these substances may adversely affect aquatic organisms. Here we expose mussels for 7 days to metformin, the most commonly prescribed anti-diabetes treatment, at a concentration of 40 μg/L and a high temperature of 20 °C. The apoptosis-related genes HSP70, CASP8, BCL2 and FAS showed variation in expression in gonadal tissue. The results suggest that complex interactions between these genes are modulating the onset of apoptotic changes such as atresia and follicle degeneration. The temperature induced apoptosis may be initiated by overexpression of CASP8. Conversely, metformin may induce apoptosis by suppressing the anti-apoptotic gene BCL2, thus promoting the process. Interestingly, apoptosis and follicle degeneration are likely FAS-mediated, following the synergistic effect of metformin and temperature. The potential of metformin to act as a non-traditional EDC, due to its impact on the reproductive system in mussels is discussed.

Original languageEnglish
Article number113011
JournalMarine Pollution Bulletin
Volume173
Issue numberPt A
DOIs
Publication statusPublished - 9 Oct 2021

Bibliographical note

Funding Information:
The authors would like to thank Dr. Darren McCabe and Lisa Jolliffe for their laboratory assistance. This research is funded by the Ministry of Research, Technology, and Higher Education (MRTHE) Republic of Indonesia through Research and Innovation in Science and Technology Project (RISET-Pro).

Funding Information:
This work was supported by Ministry of Research, Technology, and Higher Education (MRTHE) Republic of Indonesia through Research and Innovation in Science and Technology Project (RISET-Pro). The funding body has no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Keywords

  • Apoptosis
  • Metformin
  • mRNA expression
  • Multiple stressors
  • Mussels
  • Temperature

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