Abundance of estrogen receptors involved in non-canonical signaling in the dog testis.

With estrogen regulation of the reproductive system, G-protein-coupled membrane estrogen receptor (GPER) and estrogen-related receptors (ERRs) are implicated. Non-canonical receptors can bind estrogens such as environmental and pharmacological chemicals. These compounds induce rapid non-genomic pathways or receptor interaction including autoactivation. Testicular tumors occur in dogs more frequently than in other domestic animals. Also, in recent decades there were increased occurrences of various tumor types in dogs. Using qRT-PCR, Western blot and immunohistochemistry procedures in the present study, there was determination of abundance pattern of GPER, ERRα, ß and γ in dog tests when there were intratubular germ cell tumors. There was quantitation of estradiol, cyclic GMP and calcium ions (Ca2+). There were changes (P < 0.01; P < 0.001) in GPER, ERRα and ß in both mRNA transcript and protein abundances including less (P < 0.001) co-abundance of ERRγ mRNA transcript and protein. Receptors were mainly located in Leydig cells with there being receptor delocalization to the cell cytoplasm or occasionally detections in the seminiferous tubule epithelia, especially of testicular tumor tissues. There were also greater estradiol (P < 0.05) and lesser cGMP and Ca2+ concentrations in testicular tumor tissues indicating there was a disrupted sex steroid milieu and tumor cell metastasis. Results from the present study provide further evidence that ERRγ has marked actions in testicular germ cell tumor initiation and development and in further structural-functional disruptions of dog testis. Concomitantly, abundance pattern of GPER and ERRs, relative to concentrations of cGMP and Ca2+, may be an additional indicator of intratubular germ cell tumors in dogs.

Senescence and adiponectin signaling - Studies in canine testis.

BACKGROUND: The meaning of senescence for tissue physiological and pathological conditions is poorly known. Based on initial reports especially proteins and mechanisms that regulate this process are necessary to be determinate. METHODS: The main aim of the study was to investigate the presence of senescent cells in canine testicular tissue (mixed breed testes; n = 60) in relation to adiponectin signaling. In detail, new information on the senescence cell number, as well as senescence and adiponectin signaling mechanisms in cryptorchid and germ cell tumor testes were provided with the use of immunohistochemical and colorimetric analyses. RESULTS: Comparison of immunohistochemical results, in cryptorchid and tumor testes revealed increased number of senescent cells (p16 and γH2AX markers). Increased expression of adiponectin and adiponectin receptor 1, as well as extracellular signal-activated kinase (ERK1/2) in pathological testes were detected. In addition, decreased cholesterol and increased testosterone levels in tumor testis were found. CONCLUSION: The present study is the first to demonstrate the presence as well as the differences that exist in senecent cell number in mixed breed dog testes with cryptorchidism and germ cell tumor. Altered expression of adiponectin signaling and ERK1/2 signaling pathways together with altered cholesterol and testosterone levels reflect important senescence role in disturbed functions of canine testis. Moreover, the application of studied here senescence regulating molecules for detection and prevention against pathologies of the male gonad should be furtherly considered.