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Metabolic regulation is important for spermatogenesis

Nature Reviews Urology volume 9, pages 330–338 (2012)Cite this article

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Abstract

Male factor infertility is increasing in developed countries, and several factors linked to lifestyle have been shown to negatively affect spermatogenesis. Sertoli cells are pivotal to spermatogenesis, providing nutritional support to germ cells throughout their development. Sertoli cells display atypical features in their cellular metabolism; they can metabolize various substrates, preferentially glucose, the majority of which is converted to lactate and not oxidized via the tricarboxylic acid cycle. Why Sertoli cells preferentially export lactate for germ cells is not entirely understood. However, lactate is utilized as the main energy substrate by developing germ cells and has an antiapoptotic effect on these cells. Several biochemical mechanisms contribute to the modulation of lactate secretion by Sertoli cells. These include the transport of glucose through the plasma membrane, mediated by glucose transporters; the interconversion of pyruvate to lactate by lactate dehydrogenase; and the release of lactate mediated by monocarboxylate transporters. Several factors that modulate Sertoli cell metabolism have been identified, including sex steroid hormones, which are crucial for maintenance of energy homeostasis, influencing the metabolic balance of the whole body. In fact, energy status is essential for normal reproductive function, since the reproductive axis has the capacity to respond to metabolic cues.

Key Points

  • Sertoli cells have multiple roles in germ cell development, ranging from physical support and immunoprotection to the supply of nutrients and other factors

  • Germ cells have specific metabolic needs, which change during their development into spermatozoa, rendering them dependent on the nurturing provided by Sertoli cells

  • Sertoli cells utilize a number of different substrates (including glucose and fatty acids) and pathways to fulfill their metabolic requirements, as well as those of developing germ cells

  • A number of hormones and factors, such as follicle-stimulating hormone, insulin, insulin growth factor-I, epidermal growth factor, paracrine factor P-Mod-S, tri-iodothyronine, basic fibroblast growth factor, cytokines, carnitine, AMP-activated protein kinase, arachidonic acid and sex steroid hormones, are known to be metabolic modulators of Sertoli cells

  • Metabolic status is central to the regulation of the energy demands of the reproductive system, and extreme metabolic disorder conditions (such as obesity) are deleterious to reproductive function

  • The reproductive axis (hypothalamus–pituitary–testis axis) is exceptionally sensitive to energetic imbalance and disturbances of this axis severely affect Sertoli cells functions

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Figure 1: Schematic illustration of spermatogenesis.
Figure 2: Schematic illustration of Sertoli cell metabolism.

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Acknowledgements

This work was supported by the Portuguese “Fundação para a Ciência e a Tecnologia”—FCT (PTDC/QUI-BIQ/121446/2010) co-funded by FEDER via Programa Operacional Factores de Competitividade—COMPETE/QREN. L. Rato (SFRH/BD/72733/2010), M. G. Alves (SFRH/BPD/80451/2011) and A. I. Duarte (SFRH/BPD/26872/2006) were financed by FCT. P. F. Oliveira was financed by FCT through FSE and POPH funds (Programa Ciência 2008).

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  1. Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior (CICS–UBI), 6201-506, Covilhã, Portugal

    Luís Rato, Marco G. Alves, Sílvia Socorro, José E. Cavaco & Pedro F. Oliveira

  2. Centre for Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-517, Coimbra, Portugal

    Ana I. Duarte

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  1. Luís Rato
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Contributions

L. Rato and M. G. Alves researched data for the article. L. Rato, M. G. Alves and P. F. Oliviera contributed substantially to discussion of content, writing and reviewing/editing the manuscript before submission. S. Socorro, A. I. Duarte and J. E. Cavaco contributed substantially to discussion of content and reviewing/editing the manuscript before submission.

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Correspondence to Pedro F. Oliveira.

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Rato, L., Alves, M., Socorro, S. et al. Metabolic regulation is important for spermatogenesis. Nat Rev Urol 9, 330–338 (2012). https://doi.org/10.1038/nrurol.2012.77

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