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Development of peptides for targeting cell ablation agents concurrently to the Sertoli and Leydig cell populations of the testes: an approach to non-surgical sterilization

Barbara Fraser, Alex Wilkins, Sara Whiting, Mingtao Liang, Diane Rebourcet, Brett Nixon, View ORCID ProfileR. John Aitken
doi: https://doi.org/10.1101/2023.09.17.558160
Barbara Fraser
1Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia, 2308
2Pregnancy and Reproduction Program, Hunter Medical Research Institute, Kookaburra Cct, New Lambton Heights NSW, Australia 2305
3College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308
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Alex Wilkins
1Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia, 2308
2Pregnancy and Reproduction Program, Hunter Medical Research Institute, Kookaburra Cct, New Lambton Heights NSW, Australia 2305
3College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308
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Sara Whiting
1Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia, 2308
2Pregnancy and Reproduction Program, Hunter Medical Research Institute, Kookaburra Cct, New Lambton Heights NSW, Australia 2305
3College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308
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Mingtao Liang
4School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia, 2308
5College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308
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Diane Rebourcet
1Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia, 2308
2Pregnancy and Reproduction Program, Hunter Medical Research Institute, Kookaburra Cct, New Lambton Heights NSW, Australia 2305
3College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308
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Brett Nixon
1Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia, 2308
2Pregnancy and Reproduction Program, Hunter Medical Research Institute, Kookaburra Cct, New Lambton Heights NSW, Australia 2305
3College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308
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R. John Aitken
1Priority Research Centre for Reproductive Science, University of Newcastle, Callaghan, NSW, Australia, 2308
2Pregnancy and Reproduction Program, Hunter Medical Research Institute, Kookaburra Cct, New Lambton Heights NSW, Australia 2305
3College of Engineering, Science and Environment, University of Newcastle, Callaghan, NSW 2308
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  • ORCID record for R. John Aitken
  • For correspondence: John.Aitken@newcastle.edu.au
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Abstract

The surgical sterilization of cats and dogs has been used to prevent their unwanted breeding for decades, but this is an expensive and invasive procedure, and often impractical in wider contexts, for example the control of feral populations. A sterilization agent that could be administered in a single injection would not only eliminate the risks imposed by surgery but also be a much more cost-effective solution to this worldwide problem. In this study, we sought to develop a targeting peptide that would selectively bind to Leydig cells of the testes. Subsequently, after covalently attaching a cell ablation agent, Auristatin, to this peptide we aimed to apply this conjugated product (LH2Auristatin) to adult male mice in vivo, both alone and together with a previously developed Sertoli cell targeting peptide (FSH2Menadione). The application of LH2Auristatin alone resulted in an increase in DNA damage, reduced mean testes weights and mean seminiferous tubule size, along with extensive germ cell apoptosis and a reduction in litter sizes. Together with FSH2Menadione there was also an increase in embryo resorptions. These promising results were observed in around a third of all treated animals. Given this variability we discuss how these reagents might be adjusted in order to increase target cell ablation and improve their efficacy as sterilization agents.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 18, 2023.
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Development of peptides for targeting cell ablation agents concurrently to the Sertoli and Leydig cell populations of the testes: an approach to non-surgical sterilization
Barbara Fraser, Alex Wilkins, Sara Whiting, Mingtao Liang, Diane Rebourcet, Brett Nixon, R. John Aitken
bioRxiv 2023.09.17.558160; doi: https://doi.org/10.1101/2023.09.17.558160
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Development of peptides for targeting cell ablation agents concurrently to the Sertoli and Leydig cell populations of the testes: an approach to non-surgical sterilization
Barbara Fraser, Alex Wilkins, Sara Whiting, Mingtao Liang, Diane Rebourcet, Brett Nixon, R. John Aitken
bioRxiv 2023.09.17.558160; doi: https://doi.org/10.1101/2023.09.17.558160

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