The domestic pig as a model for the study of mitochondrial inheritance

Abstract

Maternal mitochondrial inheritance is a fundamental paradigm within reproductive biology, yet the molecular mechanisms which underlie this process remain poorly understood. The ubiquitin proteasome system (UPS) and branches of the autophagic pathway have been implicated in taking part in the active degradation of sperm mitochondria post-fertilization. Despite this knowledge, there remains much unknown about this process, including the cofactors and substrates involved, as well as the implications of what occurs when these systems of degradation fail. Mitochondrial inheritance research has utilized a variety of animal models. However, one model that is of particular importance, especially when attempting to link mitochondrial inheritance research to humans, is the domestic pig. Pigs offer relatively easy collection of gametes which are similar to those of humans. Furthermore, pigs are physiologically and anatomically more similar to humans than the majority of other model systems available. Porcine in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and novel cell-free systems are research tools which can be exploited to provide greater insight into the processes behind sperm mitochondrial degradation. In the future studies of mitochondrial inheritance, pigs will likely play a crucial role as an animal model system.

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Acknowledgements

We thank Professor Rodney Geisert (MU Animal Science) for the image of the porcine female reproductive tract incorporated in Figure 1, and Professor Kathy Timms (MU OBGYN & Women’s Health) for permission to use unpublished data from a joint research project (Figure 2B). We appreciate our colleagues and collaborators, past and present who have been supporting our research on sperm mitophagy. Porcine gametes for our work have been provided reliably by the NIH National Swine Resource and Research Center (NSRRC), University of Missouri.

Funding

Work in our laboratory, directly pertinent to this manuscript has been funded by Agriculture and Food Research Initiative Competitive Grant no. 2013-67015-20961. Other research in our laboratory relevant to this review has been funded by the National Institute of Food and Agriculture (NIFA), U.S. Department of Agriculture (USDA) grant number 2015-67015-23231, grant number 5 R01 HD084353-02 from NIH National Institute of Child and Human Development, and seed funding from the Food for the twenty-first Century Program of the University of Missouri.

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Zuidema, D., Sutovsky, P. The domestic pig as a model for the study of mitochondrial inheritance. Cell Tissue Res 380, 263–271 (2020). https://doi.org/10.1007/s00441-019-03100-z

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Keywords

  • Mitochondria
  • mtDNA
  • Inheritance
  • Ubiquitin
  • Autophagy
  • Proteasome
  • Sperm
  • Oocyte
  • Fertilization