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  • Review Article
  • Published:

Energy metabolism and fertility—a balance preserved for female health

Key Points

  • Metabolic and reproductive pathways are tightly associated, and this relationship has been conserved throughout evolution

  • Reproductive disorders can lead to changes in metabolic function

  • Similarly, metabolic disorders can underlie changes in reproductive function

  • Hormone replacement therapy for reproductive disorders might also have beneficial effects on energy metabolism

Abstract

In female animals, energy metabolism and fertility are tightly connected, and reciprocally regulated. However, the relative contributions of metabolic and reproductive pathways have changed over the course of evolution. In oviparous animals, metabolic factors take precedence over fertility, enabling egg production to be inhibited in a nutritionally poor environment. By contrast, in placental mammals, the opposite occurs: the need to feed a developing embryo and neonate forces metabolic pathways to adapt to these reproductive needs. This physiological necessity explains why in female mammals alterations of gonadal activity, including age-dependent cessation of ovarian functions, are associated with a disruption of metabolic homeostasis and consequent inflammatory reactions that trigger the onset of metabolic, cardiovascular, skeletal and neural pathologies. This Review discusses how metabolic homeostasis and reproductive functions interact to optimize female fertility and explains the pathogenic mechanisms underlying the disordered energy metabolism associated with human ovarian dysfunction owing to menopause, polycystic ovary syndrome and Turner syndrome. Finally, this article highlights how hormone replacement therapy might aid the restoration of metabolic homeostasis in women with ovarian dysfunction.

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Figure 1: The mutual control of nutritional status and reproduction throughout evolution.
Figure 2: ERα in hypothalamic circuits regulates energy metabolism and reproduction.
Figure 3: Reciprocal regulation of energy metabolism and reproduction.

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Acknowledgements

The authors are sincerely grateful to Enzo Nisoli for his important, thoughtful suggestions and critical assessment of the manuscript, and to the European Research Council (ERC-Advanced Grant 322977 and INMiND Collaborative Project FP7-HEALTH-011.2.2.1-2 to A. Maggi) and Pfizer (grant IIR WS897258 to A. Maggi) for their research support.

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All authors researched the data for the article and contributed substantially to discussions of its content. A. Maggi wrote the manuscript, and S. Della Torre, V. Benedusi and R. Fontana reviewed and/or edited the manuscript before submission.

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Correspondence to Adriana Maggi.

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A. Maggi declares that she has received research funding from Pfizer. The other authors declare no competing interests.

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Torre, S., Benedusi, V., Fontana, R. et al. Energy metabolism and fertility—a balance preserved for female health. Nat Rev Endocrinol 10, 13–23 (2014). https://doi.org/10.1038/nrendo.2013.203

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