Abstract

Androgen receptor signaling pathway is necessary to complete spermatogenesis in testes. Difference between androgen binding location in Sertoli cell classifies androgen receptor signaling pathway into classical signaling pathway and non-classical signaling pathway. As the only somatic cell type in seminiferous tubule, Sertoli cells are under androgen receptor signaling pathway regulation via androgen receptor located in cytoplasm and plasma membrane. Androgen receptor signaling pathway is able to regulate biological processes in Sertoli cells as well as germ cells surrounded between Sertoli cells. Our review will summarize the major discoveries of androgen receptor signaling pathway in Sertoli cells and the paracrine action on germ cells. Androgen receptor signaling pathway regulates Sertoli cell proliferation and maturation, as well as maintain the integrity of blood-testis barrier formed between Sertoli cells. Also, Spermatogonia stem cells achieve a balance between self-renewal and differentiation under androgen receptor signaling regulation. Meiotic and post-meiotic processes including Sertoli cell - Spermatid attachment and Spermatid development are guaranteed by androgen receptor signaling until the final sperm release. This review also includes one disease related to androgen receptor signaling dysfunction named as androgen insensitivity syndrome. As a step further ahead, this review may be conducive to develop therapies which can cure impaired androgen receptor signaling in Sertoli cells.

Highlights

  • Male infertility is currently a major problem worldwide and causes substantial psychological and social distress [1]

  • The blood-testis barrier (BTB) appears to be present in this model under microscopic examination, it is incomplete as we found biotin enter into adluminal area with the help of biotin tracer [127]

  • Both classical and non-classical androgen receptor signaling pathway are essential for spermatogenesis

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Summary

INTRODUCTION

Male infertility is currently a major problem worldwide and causes substantial psychological and social distress [1]. SCs function like a nurse to take good care of spermatogenesis [12] These functions of SCs are regulated by both extrinsic and intrinsic factors. We review androgen receptor (AR) signaling pathway in SCs, a pathway that provides an excellent example of a combination of extrinsic and intrinsic regulation. It is necessary to review current work about androgen receptor signaling pathway in SCs and put forward suggestions for future studies. We surveyed articles in the PubMed database using the following search terms: androgen receptor*, Sertoli cell*, spermatogonia*, maturation and differentiation*, spermatogenesis*, meiosis*, spermatid* and androgen-insensitive syndrome*. We will present this review at the cellular/molecular level in six parts: SC proliferation and maturation, SSC self-renewal and differentiation, spermatocyte meiosis, BTB integrity maintenance, Sertoli cell - Spermatid adhesion, and sperm release (Figure 1). We discuss androgen insensitive syndrome (AIS), briefly reviewing its pathogenesis, diagnosis and offering suggestions for better diagnosis and treatment

STRUCTURE OF ANDROGEN RECEPTOR
OVERVIEW OF ANDROGEN RECEPTOR SIGNALING PATHWAY IN SERTOLI CELLS
Classical Signaling Pathway
Non-Classical Signaling Pathway
Role of AR Mediated Signaling in Sertoli Cell Proliferation and Maturation
Role of AR Mediated Signaling in Spermatocytes Meiosis
Role of AR Mediated Signaling in Maintenance of Blood-Testis Barrier
Findings
DISCUSSION
CONCLUSION AND PERSPECTIVE
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