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Creatine metabolism in the uterus: potential implications for reproductive biology

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Abstract

Creatine is an amino acid derivative synthesized from arginine, glycine and methionine. It serves as the substrate for the creatine kinase system, which is vital for maintaining ATP levels in tissues with high and fluctuating energy demand. There exists evidence that the creatine kinase system operates in both the endometrial and myometrial layers of the uterus. While use and regulation of this system in the uterus are not well understood, it is likely to be important given uterine tissues undergo phases of increased energy demand during certain stages of the female reproductive cycle, pregnancy, and parturition. This review discusses known adaptations of creatine metabolism in the uterus during the reproductive cycle (both estrous and menstrual), pregnancy and parturition, highlighting possible links to fertility and the existing knowledge gaps. Specifically, we discuss the adaptations and regulation of uterine creatine metabolite levels, cell creatine transport, de novo creatine synthesis, and creatine kinase expression in the various layers and cell types of the uterus. Finally, we discuss the effects of dietary creatine on uterine metabolism. In summary, there is growing evidence that creatine metabolism is up-regulated in uterine tissues during phases where energy demand is increased. While it remains unclear how important these adaptations are in the maintenance of healthy uterine function, furthering our understanding of uterine creatine metabolism may uncover strategies to combat poor embryo implantation and failure to conceive, as well as enhancing uterine contractile performance during labor.

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Funding

SE was an NHMRC Peter Doherty Early Career Research Fellow during the completion of this review.

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Authors and Affiliations

  1. Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences Deakin University, Geelong, VIC, Australia

    Mamatha Philip, Rodney J. Snow & Paul A. Della Gatta

  2. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Australia

    Nadia Bellofiore & Stacey J. Ellery

  3. Department of Obstetrics and Gynecology, Monash University, Melbourne, Australia

    Nadia Bellofiore & Stacey J. Ellery

Authors
  1. Mamatha Philip
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  2. Rodney J. Snow
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  3. Paul A. Della Gatta
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  4. Nadia Bellofiore
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  5. Stacey J. Ellery
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Contributions

SE and RS developed the structure of the review; MP drafted the review. All authors were involved in critically evaluating drafts of manuscript and provided final approval of the submitted version to be published.

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Correspondence to Stacey J. Ellery.

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The authors declare that they have no conflict of interest.

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Handling Editor: J. D. Wade.

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Philip, M., Snow, R.J., Gatta, P.A.D. et al. Creatine metabolism in the uterus: potential implications for reproductive biology. Amino Acids 52, 1275–1283 (2020). https://doi.org/10.1007/s00726-020-02896-3

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  • DOI: https://doi.org/10.1007/s00726-020-02896-3

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