Ageing and inflammation in the male gonad

1.MATZKIN ME; GONZALEZ-CALVAR SI, MAYERHOFER A, CALANDRA RS, FRUNGIERI MB

Bethesda, Maryland

Workshop; Cellular and Molecular Aging of the Reproductive System NIH-NIA; 2018

The National Institute of Aging dependiente del The National Institute of Health (NIA-NIH),

In order to investigate a potential relation between aging and inflammatory processes in the male gonad, we used well-established mouse models with alterations of the somatotropic signaling and longevity. We described that the testes of short-lived mice with accelerated aging (growth hormone-transgenic mice) show a significant increase in cyclooxygenase 2 expression, PGD2 production, lipid peroxidation, antioxidant enzymes expression, local macrophages and TUNEL-positive germ cells numbers, and the levels of both pro-caspase-3 and cleaved caspase-3. In contrast, these parameters showed a reduction in testes of long-lived mice with delayed aging (growth hormone releasing hormone-knockout and Ames dwarf mice). Our data provide novel evidence that longevity confers anti-inflammatory, anti-oxidant and anti-apoptotic capacities to the adult testis. Oppositely, short-lived mice with accelerated aging suffer testicular inflammatory, oxidative and apoptotic processes. These results were further verified using a physiological model of aging without mutations in the GH/IGF-1 pathway. Raised levels of inflammatory markers were found in testes of aged Syrian hamsters. This species is a seasonal breeder in which the progressive increase in testicular lipid peroxidation with age is inversely associated with the gonadal levels of melatonin. The latter allows us to speculate about an antioxidant role of this neurohormone in the testis.Interestingly, in testes of adult men with idiopathic infertility, we have described similar findings to those observed in the testis of aged rodents. In view of these observations, it is possible to conclude that there is a clear parallelism between the changes taking place in the aged-testis and the alterations that occur in gonads of young adult infertile men.