Paracrine Mechanisms Involved in the Control of Early Stages of Mammalian Spermatogenesis

Pellegrino Rossi,Susanna Dolci

doi:10.3389/fendo.2013.00181

Abstract

Within the testis, Sertoli-cell is the primary target of pituitary FSH. Several growth factors have been described to be produced specifically by Sertoli cells and modulate male germ cell development through paracrine mechanisms. Some have been shown to act directly on spermatogonia such as GDNF, which acts on self-renewal of spermatogonial stem cells (SSCs) while inhibiting their differentiation; BMP4, which has both a proliferative and differentiative effect on these cells, and KIT ligand (KL), which stimulates the KIT tyrosine-kinase receptor expressed by differentiating spermatogonia (but not by SSCs). KL not only controls the proliferative cycles of KIT-positive spermatogonia, but it also stimulates the expression of genes that are specific of the early phases of meiosis, whereas the expression of typical spermatogonial markers is down-regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in fetal gonocytes and in post-natal spermatogonia through the induction of the RNA-binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in Sertoli cells, controls both SSCs differentiation through KIT induction and NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through STRA8 upregulation.

Highlights

Within the testis, Sertoli-cell is the primary target of pituitary FSH
BRIEF INTRODUCTION: PARACRINE CONTROL OF FETAL MALE GERM CELL DEVELOPMENT The control of the germ cell fate by paracrine factors secreted by the surrounding somatic environment already starts in the fetal life in the period of germ cell specification, independently from the influence of the hypothalamic-pituitary axis
In the same period in which Fibroblast Growth factor 9 (FGF9) is expressed during testis determination, Sertoli cells produce an enzyme, CYP26B1, which degrades Retinoic Acid (RA) of mesonephric origin, in order to block Stimulated by Retinoic Acid 8 (STRA8) expression, and, as a consequence, to prevent premature gonocyte entry into meiosis [17,18,19,20]

Summary

Introduction

Sertoli-cell is the primary target of pituitary FSH. Several growth factors have been described to be produced by Sertoli cells and modulate male germ cell development through paracrine mechanisms. KIT is universally considered the most important marker that distinguishes differentiating spermatogonia from their undifferentiated precursors, including SSCs. paracrine factors in the testicular environment that stimulate KIT expression in mitotic germ cells play an essential role for the start of spermatogenesis at puberty.

Results

Conclusion