Testicular developmental impairment caused by Flutamide-induced and DEHP-induced cryptorchid rat models is mediated by excessive apoptosis and deficient autophagy.

Testicular developmental impairment caused by Flutamide-induced and DEHP-induced cryptorchid rat models is mediated by excessive apoptosis and deficient autophagy.

Toxicol Mech Methods. 2018 Apr 02;:1-39

Authors: Wei Y, Zhou Y, Tang XL, Liu B, Shen LJ, Long CL, Lin T, He DW, Wu SD, Wei GH

Abstract
BACKGROUND: Cryptorchidism is a common condition of childhood, and it is known to impair fertility potential. However, the underlying mechanisms remain unclear.
METHODS: This study constructed two cryptorchid rat models to investigate the roles of apoptosis and autophagy in testicular impairment induced by cryptorchidism. Pregnant rats were randomly divided into three groups. Group I: non-treated rats were used as controls. Group II: injected with drug Flutamide (Flu) 25 mg/kg/bw/d from Gestation Day (GD) 11-19. Group III: daily intragastric administration of 750 mg/kg/bw/d di-2-ethylhexylphosphate (DEHP) from GD 7-19. The cubs were feed normally and the testes were excised on postnatal day (PND) 30.
RESULTS: Our results demonstrated cryptorchidism models induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate, decreased testosterone and severe testicular damage in histomorphology. Intriguingly, the level of apoptosis marker FAS, Cytochrome C and caspase-3 increased in Flu-induced and DEHP-induced groups. DEHP-induced treatment simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62. Significant decrease of autophagy gene (LC3-II and p62) expression is found in Flu-induced rats testes.
CONCLUSION: Taken together, deficient autophagy is involved in testicular spermatogenesis damage of cryptorchidism rats. And this autophagy defect is caused by deficient degradation.

PMID: 29606031 [PubMed - as supplied by publisher]

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