Triphenyltin Chloride Delays Leydig Cell Maturation During Puberty in Rats

Triphenyltin chloride (TPT) is present in a wide range of human foods. TPT could disrupt testis function as a potential endocrine disruptor of Leydig cells. However, the effect of TPT on pubertal Leydig cell development is still unclear. The objective of the current study was to explore whether exposure to TPT affected Leydig cell developmental process and to clarify the underlying mechanisms. Male Sprague-Dawley rats at 35 days of age were randomly divided into four groups and received normal corn oil (control), 0.5, 1, or 2 mg/kg/day TPT for 18 days. Immature Leydig cells isolated from 35-day-old rat testes were treated with TPT (10 and 100 nM) for 24 h in vitro. In vivo exposure to ≥0.5 mg/kg TPT lowered serum testosterone levels and lowered Star mRNA. TPT at 2 mg/kg also lowered Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3 as well as pAKT1/AKT1, pAKT2/AKT2, and pERK1/2/ERK1/2 ratios. In vitro exposure to TPT (100 nM) increased ROS production and induced cell apoptosis rate in rat immature Leydig cells. In conclusion, TPT exposure disrupts Leydig cell development possibly via interfering with the phosphorylation of AKT1, AKT2, and ERK1/2 kinases

Fibroblast Growth Factor 1 Promotes Rat Stem Leydig Cell Development

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