Fibroblast Growth Factor 1 Promotes Rat Stem Leydig Cell Development.

Lanlan Chen,Ren-Shan Ge,Xianwu Chen,Lubin Xie,Yiyan Wang,Xiaoheng Li,Yong Chen,Tiantian Song,Yao Lv,Huitao Li,Leikai Ma,Xingwang Li,Linchao Li

doi:10.3389/fendo.2019.00118

Abstract

Fibroblast growth factor 1 (FGF1) is reported to be expressed in the testis. How FGF1 affects stem Leydig cell development remains unclear. Here, we report the effects of FGF1 on rat stem Leydig cell development in an ethane dimethane sulfonate (EDS)-treated model. FGF1 (100 ng/testis) significantly increased serum testosterone level, increased PCNA-positive Leydig cell percentage and Leydig cell number, but down-regulated the expression of Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd11b1 in Leydig cells per se, after its daily intratesticular injection from post-EDS day 14 for 14 days. Primary culture of the seminiferous tubules showed that FGF1 stimulated EdU incorporation to stem Leydig cells but blocked the differentiation into the Leydig cell lineage, possibly via FGFR1-mediated mechanism. In conclusion, FGF1 promotes stem Leydig cell proliferation but blocks its differentiation.

Highlights

The adult Leydig cell (ALC) is a cell type in the mammalian testis that secretes androgen
We identified that stem Leydig cells (SLCs) express higher level of Fgfr1 and
Fibroblast growth factor 1 (FGF1) is able to increase the proliferation of SLCs, populating Leydig cell number during its earlier stage of regeneration in an ethane dimethane sulfonate (EDS)-treated model

Summary

INTRODUCTION

The adult Leydig cell (ALC) is a cell type in the mammalian testis that secretes androgen. In several mammalian species, including rats, when males are administered with ethane dimethane sulfonate (EDS), a chemical that only kills ALCs in the testis, a new population of ALCs develops [1, 2] These newly-formed ALCs arise from the undifferentiated SLCs [3]. On day 21 after EDS dosing, progenitor cells develop as shown by the expression of the Leydig cell lineage biomarkers: lutropin-choriogonadotropic hormone receptor (LHCGR), high-density lipoprotein receptor (SCARB1), steroidogenic acute regulatory protein (STAR), cholesterol side-chain-cleaving enzyme (CYP11A1), 3β- 3β-hydroxysteroid dehydrogenase/ [5]- [4]isomerase type I (HSD3B1), cytochrome 17α-hydroxylase/17,20 lyase/17,20 desmolase (CYP17A1), and steroid 5α-reductase 1 (SRD5A1) [4, 5]. We interrogate FGF1 roles on SLC development and dissect the underlying mechanism

MATERIALS AND METHODS

RESULTS

DISCUSSION