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Exposure to Endosulfan can result in male infertility due to testicular atrophy and reduced sperm count

View Article: PubMed Central - PubMed

ABSTRACT

Endosulfan (ES) is a widely used organochlorine pesticide and is speculated to be detrimental to human health. However, very little is known about mechanism of its genotoxicity. Using mouse model system, we show that exposure to ES affected physiology and cellular architecture of organs and tissues. Among all organs, damage to testes was extensive and it resulted in death of different testicular-cell populations. We find that the damage in testes resulted in qualitative and quantitative defects during spermatogenesis in a time-dependent manner, increasing epididymal reactive oxygen species levels, affecting sperm chromatin integrity. This further culminated in reduced number of epididymal sperms and actively motile sperms. Finally, we show that ES exposure affected fertility in male but not in female mice. Therefore, we demonstrate that ES exerts pathophysiological changes in mice, induces testicular atrophy, affects spermatogenesis, reduces quantity and vigour of epididymal sperm and leads to infertility in males.

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Endosulfan-induced cell death is specific to testes. (a) TUNEL assay showing DNA fragmentation in testicular cells following ES treatment (3 mg/kg) in male mice. Green colour indicates methyl green counter-stained nuclei and the brown spots are broken DNA stained with diaminobenzidine (DAB). Control sections are devoid of TUNEL-positive cells. (b) TUNEL assay performed on sections obtained at 11th day post-ES treatment showing TUNEL-positive cells. indicating persisting cell death. (c) TUNEL assay showing no stained cells in control and ES-treated mice lungs (1st day). (d) TUNEL assay in brain sections showing absence of positively stained cells (×20).
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fig3: Endosulfan-induced cell death is specific to testes. (a) TUNEL assay showing DNA fragmentation in testicular cells following ES treatment (3 mg/kg) in male mice. Green colour indicates methyl green counter-stained nuclei and the brown spots are broken DNA stained with diaminobenzidine (DAB). Control sections are devoid of TUNEL-positive cells. (b) TUNEL assay performed on sections obtained at 11th day post-ES treatment showing TUNEL-positive cells. indicating persisting cell death. (c) TUNEL assay showing no stained cells in control and ES-treated mice lungs (1st day). (d) TUNEL assay in brain sections showing absence of positively stained cells (×20).

Mentions: To assess whether ES induces cell death in testes, TUNEL assay was performed on testicular section of mice treated with ES (3 mg/kg; 1, 11 day). Results showed TUNEL-positive cells among spermatogonial mother cells, spermatocytes and spermatids 24 h post-ES treatment (Figure 3a). Interestingly, despite pathophysiological changes, DNA damage response and changes in the levels of apoptotic proteins (RS and SCR, unpublished observations), we could not observe TUNEL-positive cells in lungs on ES treatment (Figure 3c). This could be due to the limitation of scoring apoptosis in lungs as apoptotic cells would be cleared much efficiently and swiftly in lungs than in other organs.21 TUNEL-positive cells were repeatedly observed in testes, when experiment was repeated 11 days after ES treatment, suggesting persistent DNA damage (Figure 3b). Brain sections did not show any sign of apoptosis following ES treatment, justifying the observed intact architecture in histological studies (Figure 3d).


Exposure to Endosulfan can result in male infertility due to testicular atrophy and reduced sperm count
Endosulfan-induced cell death is specific to testes. (a) TUNEL assay showing DNA fragmentation in testicular cells following ES treatment (3 mg/kg) in male mice. Green colour indicates methyl green counter-stained nuclei and the brown spots are broken DNA stained with diaminobenzidine (DAB). Control sections are devoid of TUNEL-positive cells. (b) TUNEL assay performed on sections obtained at 11th day post-ES treatment showing TUNEL-positive cells. indicating persisting cell death. (c) TUNEL assay showing no stained cells in control and ES-treated mice lungs (1st day). (d) TUNEL assay in brain sections showing absence of positively stained cells (×20).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4979443&req=5

fig3: Endosulfan-induced cell death is specific to testes. (a) TUNEL assay showing DNA fragmentation in testicular cells following ES treatment (3 mg/kg) in male mice. Green colour indicates methyl green counter-stained nuclei and the brown spots are broken DNA stained with diaminobenzidine (DAB). Control sections are devoid of TUNEL-positive cells. (b) TUNEL assay performed on sections obtained at 11th day post-ES treatment showing TUNEL-positive cells. indicating persisting cell death. (c) TUNEL assay showing no stained cells in control and ES-treated mice lungs (1st day). (d) TUNEL assay in brain sections showing absence of positively stained cells (×20).
Mentions: To assess whether ES induces cell death in testes, TUNEL assay was performed on testicular section of mice treated with ES (3 mg/kg; 1, 11 day). Results showed TUNEL-positive cells among spermatogonial mother cells, spermatocytes and spermatids 24 h post-ES treatment (Figure 3a). Interestingly, despite pathophysiological changes, DNA damage response and changes in the levels of apoptotic proteins (RS and SCR, unpublished observations), we could not observe TUNEL-positive cells in lungs on ES treatment (Figure 3c). This could be due to the limitation of scoring apoptosis in lungs as apoptotic cells would be cleared much efficiently and swiftly in lungs than in other organs.21 TUNEL-positive cells were repeatedly observed in testes, when experiment was repeated 11 days after ES treatment, suggesting persistent DNA damage (Figure 3b). Brain sections did not show any sign of apoptosis following ES treatment, justifying the observed intact architecture in histological studies (Figure 3d).

View Article: PubMed Central - PubMed

ABSTRACT

Endosulfan (ES) is a widely used organochlorine pesticide and is speculated to be detrimental to human health. However, very little is known about mechanism of its genotoxicity. Using mouse model system, we show that exposure to ES affected physiology and cellular architecture of organs and tissues. Among all organs, damage to testes was extensive and it resulted in death of different testicular-cell populations. We find that the damage in testes resulted in qualitative and quantitative defects during spermatogenesis in a time-dependent manner, increasing epididymal reactive oxygen species levels, affecting sperm chromatin integrity. This further culminated in reduced number of epididymal sperms and actively motile sperms. Finally, we show that ES exposure affected fertility in male but not in female mice. Therefore, we demonstrate that ES exerts pathophysiological changes in mice, induces testicular atrophy, affects spermatogenesis, reduces quantity and vigour of epididymal sperm and leads to infertility in males.

No MeSH data available.


Related in: MedlinePlus