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A local autocrine axis in the testes that regulates spermatogenesis

Nature Reviews Endocrinology volume 6, pages 380–395 (2010)Cite this article

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Abstract

Spermiation—the release of mature spermatozoa from Sertoli cells into the seminiferous tubule lumen—occurs by the disruption of an anchoring device known as the apical ectoplasmic specialization (apical ES). At the same time, the blood–testis barrier (BTB) undergoes extensive restructuring to facilitate the transit of preleptotene spermatocytes. While these two cellular events take place at opposite ends of the Sertoli cell epithelium, the events are in fact tightly coordinated, as any disruption in either process will lead to infertility. A local regulatory axis exists between the apical ES and the BTB in which biologically active laminin fragments produced at the apical ES by the action of matrix metalloproteinase 2 can regulate BTB restructuring directly or indirectly via the hemidesmosome. Equally important, polarity proteins play a crucial part in coordinating cellular events within this apical ES–BTB–hemidesmosome axis. Additionally, testosterone and cytokines work in concert to facilitate BTB restructuring, which enables the transit of spermatocytes while maintaining immunological barrier function. Herein, we will discuss this important autocrine-based cellular axis that parallels the hormonal-based hypothalamic–pituitary–testicular axis that regulates spermatogenesis. This local regulatory axis is the emerging target for male contraception.

Key Points

  • The apical ectoplasmic specialization–BTB (blood–testis barrier)–hemidesmosome axis, a novel functional axis in the testis, coordinates events occurring at opposite ends of the seminiferous epithelium during spermatogenesis

  • To maintain immunological barrier function at the BTB during the transit of spermatocytes, 'new' tight junction fibrils are assembled below migrating spermatocytes before 'old' tight junction fibrils are disassembled

  • Protein endocytosis, recycling, transcytosis and endosome-mediated or ubiquitin-mediated protein degradation play a critical part in the homeostasis of this apical ectoplasmic specialization–BTB–hemidesmosome functional axis

  • Polarity proteins are important regulators of endocytic vesicle-mediated protein trafficking events in the seminiferous epithelium during spermatogenesis

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Figure 1: Cross-section of a mammalian seminiferous tubule, which is composed of the seminiferous epithelium constituted by Sertoli cells and germ cells at different stages of their development.
Figure 2: Anatomy of the seminiferous epithelium in the mammalian testis.
Figure 3: Structural domains of a typical laminin chain.
Figure 4: The apical ES–BTB–hemidesmosome functional axis in the testis.
Figure 5: Polarity protein complexes establish cell polarity.
Figure 6: Role of polarity proteins and nonreceptor protein kinases in the apical ES–BTB functional axis.
Figure 7: Role of the TBC in apical ES dynamics during spermiogenesis.

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Acknowledgements

We thank current and past members of our laboratory for their investigations and discussions which have helped to form the basis of this article. Studies performed in the authors' laboratory were supported by grants from the National Institutes of Health (NICHD, R01 HD056034 and U54 HD029990 Project 5 to C. Y. C; and R03 HD061401 to D. D. M).

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  1. The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, 1230 York Avenue, New York, 10065, NY, USA

    C. Yan Cheng & Dolores D. Mruk

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Correspondence to C. Yan Cheng.

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Cheng, C., Mruk, D. A local autocrine axis in the testes that regulates spermatogenesis. Nat Rev Endocrinol 6, 380–395 (2010). https://doi.org/10.1038/nrendo.2010.71

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