A Short-Term Exposure to Tributyltin Blocks Leydig Cell Regeneration in the Adult Rat Testis

Abstract

Background: Tributyltin (TBT) is widely used as an antifouling agent that may cause reproductive toxicity. The mechanism of TBT on Leydig cell development is still unknown. The objective of the present study was to investigate whether a brief exposure to low doses of TBT permanently affects Leydig cell development and to clarify the underlying mechanism.Methods: Adult male Sprague Dawley rats were randomly assigned into four groups and gavaged normal saline (control), 0.1, 1.0, or 10.0 mg/kg/day TBT for a consecutive 10 days, respectively. At the end of TBT treatment, all rats received a single intraperitoneal injection of 75 mg/kg ethane dimethane sulfonate (EDS) to eliminate all of adult Leydig cells. Leydig cells began a developmental regeneration process on post-EDS day 35. The Leydig cell regeneration was evaluated by measuring serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels on post-EDS day 7, 35, and 56, the expression levels of Leydig cell genes, Leydig cell morphology and number and proliferation on post-EDS day 56.Results: TBT significantly reduced serum testosterone levels on post-EDS day 35 and 56 and increased serum luteinizing hormone and follicle-stimulating hormone levels on post-EDS day 56 at ≥1 mg/kg/day. Immunohistochemical staining showed that there were fewer regenerated Leydig cells in the TBT-treated testis on post-EDS day 56. Further study demonstrated that the mRNA or protein levels of Leydig (Lhcgr, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3) and Sertoli cells (Fshr, Dhh, and Sox9) were significantly down-regulated in the TBT-treated testes when compared to the control. Immunofluorescent staining showed that TBT inhibited Leydig cell proliferation as judged by the reduced number of proliferating cyclin nuclear antigen-positive Leydig cells on post-EDS day 35.Conclusion: The present study demonstrated that a short-term TBT exposure blocked Leydig cell developmental regeneration process via down-regulating steroidogenesis-related proteins and inhibiting the proliferation of Leydig cells.

Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis

“…Leydig cells in the testis interstitial compartment contribute 95–99% of circulatory testosterone ( Wu et al, 2017 ). Testosterone biosynthesis is catalyzed by SCARB1, STAR, CYP11A1, 3β-HSD, CYP17A1, and 17β-HSD3 ( Wang et al, 2011 ), which gets promoted when LH binds to LHCGR on its surface ( Melsert et al, 1991 ; Foster, 1996 ; Zhang et al, 2018 ).…”

“…Of the various toxicities of DBTCl, it has been reported to suppress testosterone production induced by tropic stimulation, thereby demonstrating its negative effects on Leydig cells ( Nakajima et al, 2005 ; Brown et al, 2017 ; Furukawa et al, 2017 ; Milton et al, 2017 ; Zhang et al, 2018 ). Another organotin, tributyltin chloride (TBT), has been demonstrated to block Leydig cell developmental regeneration in the adult rat testis ( Wu et al, 2017 ); therefore it is worth wondering whether DBTCl has the similar effects as both TBT and DBTCl are organotins. Thus, the present study was conducted to investigate the effects of DBTCl on Leydig cell developmental regeneration, using the EDS-induced rat Leydig cell developmental regeneration model.…”

“…Both TBT and DBTCl are organotins, and it has been demonstrated that a short-term exposure to TBT blocks Leydig cell developmental regeneration in the adult rat testis ( Wu et al, 2017 ), from which it is speculated that DBTCl has similar effects. The present study testifies the hypothesis and finds that DBTCl retards Leydig cell developmental regeneration via downregulating steroidogenesis-related enzymes at both the gene and protein levels, inhibiting Leydig cell proliferation and impairing Sertoli cell function and development.…”

“…Leydig cells in the testis interstitial compartment contribute 95–99% of circulatory testosterone ( Wu et al, 2017 ). Testosterone biosynthesis is an enzyme-controlled steroidogenic process.…”

miR-205 Expression Elevated With EDS Treatment and Induced Leydig Cell Apoptosis by Targeting RAP2B via the PI3K/AKT Signaling Pathway

“…Previous studies reported that EDS could selectively ablate all the differentiated LCs in the rat testis (Sharpe et al, 1990;Morris et al, 1997;Wu et al, 2017). The blank control (not contain DMSO), 0 mg/mL EDS, and 1.0 mg/mL EDS was added to the culture solution (Yu et al, 2017).…”