Studies On Effects Of Aging On Spermatogenesis And Its Mechanism In Men And Mice

ObjectiveThe present study was to investigate the age-related changes of testes and spermatogenesis in men and mice, to detect the changes of proliferation and apoptosis in spermatogenic cells with aging in men and to discuss the possible mechanism of impaired spermatogenesis. Besides, this study was also designed to investigate the changes of aging mouse sperm functional parameters and fertility potential by using Kunming mouse model.Materials and MethodsTesticular specimens were obtained by orchiectomy from 25 aged men with advanced prostate cancer and 8 young men with unexpected death, which served as controls. The aged subjects were categorized into two age groups (A group: 54-69 years, n=12 and B group: 70-88 years, n=13). The morphological changes of testes were observed by light microscope and transmission electron microscope (TEM). The expression of proliferating cell nuclear antigen (PCNA) of spermatogenic cells was evaluated. The terminal deoxynucleotidyl transferase-mediated d-UTP biotin nick end labeling (TUNEL) technique was used to identify apoptosis of spermatogenic cells.Testicular specimens and spermatogozoa of caput epididymides and cauda epididymides were obtained from Kuming mice aged 6 months (n=15) and 18 months (n=15). The histological changes of testes were observed. Sperm parameters including sperm density, viability, motility and normal morphological rate were recorded. The fertility potential and embryo developmental competence were performed by in vitrofertilization (IVF) and embryo culture.Results1. The age-related changes in human testes were characterized by a high incidence of spermatogenic arrest, impaired spermatogenesis, increased thickness of tubular boundary tissue and sclerosed seminiferous tubules. The mean number of Sertoli cells per seminferous tubule in aged testes was lower than that in the control (P<0.01). The mean ratio of spermatogonia to Sertoli cells in aged testes was unchanged (P>0.05). The ratio of primary spermatocytes to Sertoli cells in B group was lower than that in the control (,P<0.05). The ratios of round spermatids and elongated spermatids to Sertoli cells in aged testes were decreased than those in the control CP0.001).2. The proliferative index in B group was lower than that in the control and A group (P0.01). The apoptotic index of B group was greater than that in the control (P<0.01). The ratio of proliferation to apoptosis (PI/AI) in B group was decreased comparing with that in the control and A group (P<0.01).3. The histological changes of testes in aged mice were mainly seminiferous tubule atrophy and hypospermatogenesis. The mean ratios of spermatogonia and primary spermatocytes to Sertoli cells were equal to those of the control (P>0.05). The ratios of round spermatids and elongated spermatids to Sertoli cells were significantly lower in aged mice than in young mice (P<0.01).4. Sperm density and motility in epididymides in aged mice were decreased comparing with those in the control (P0.05). The fertilization rate and embryo developmental rate of aged group were lower than those in the control (P0.01).Conclusions1. The histological changes of testes in aged men were characterized by seminiferous tubule atrophy and hypospermatogenesis.2. Spermatogenic cells in the older group (70-88 years) showed the decreased proliferation and accelerated apoptosis. The imbalance between spermatogenic cell proliferation and apoptosis would partly cause impaired spermatogenesis.3. The age-related changes of testes in mice were mainly spermatogenic arrest and hypospermatogenesis. Changes of sperm quality and quantity in aged mice indicated aging influenced spermatogenesis in testes and sperm maturation in epididymides.