Slow release gonadotropin releasing hormone (GnRH) agonist implants are frequently used for contraception in male dogs. Although the effects are fully reversible, there is still concern about the safety of the implant's mode of action. Addressing this, we investigated cellular stress and androgen receptor signaling during downregulation and recovery. Testicular tissues were sampled from dogs castrated at different time points after GnRH implant removal and compared with untreated controls. Androgen receptor (AR), hypoxia-inducible factor 1 (HIF1A) and heat shock proteins HSP72, HSP73, HSPA2, HSP90AA1 and HSP90AB1 were investigated by qPCR, and AR, HSP72, HSP73 and HSP90 immunohistochemically. While AR, HIF1A and HSP70 were upregulated at mRNA level, HSPA8, HSPA2 and HSP90AA1 expression were downregulated during spermatogenic arrest; HSP90AB1 expression did not change. Immunohistochemistry verified AR-expression in Sertoli, peritubular and Leydig cells, occasionally also in spermatogonia. Stress-inducible HSP72 was occasionally detected, while constitutive HSP73 and HSP90 were abundantly expressed by germ cells. Our results were similar with studies on seasonal breeders such as pine voles, geese, fish and soft-shelled turtles. Accordingly, GnRH implants did not impose additional cellular stress on testicular cells when compared with natural recrudescence. Since comparative data on HIF1α is scarce, we cannot draw conclusions about hypoxic conditions.
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