Aging of male germ cells
Description: Male germ cells are made on an ongoing basis in the testes of adult non-seasonal mammals. Little is known about how the quality of sperm is affected by advancing age. Do spermatogonia that divide to produce subsequent generations of germ cells accumulate damage as years go by? In man, there is an increasing rate of abnormalities in chromosomes with aging. There is a strong correlation between the age of the male partner and decreased sperm motility and normal morphology, decreased pregnancy rates, increased time to pregnancy, and higher incidences of schizophrenia and autism. Yet, the lack of robust prospective studies makes it difficult to draw firm conclusions from human data. The BN rat is an excellent model to study the effects of aging on the male reproductive system. We have found that during aging there are clear effects on progeny outcome, on sperm morphology and motility, and on the ability of sperm to withstand oxidative stress. However, the underlying factors that result in these clear age related effects are not clear. We hypothesize that, during the process of aging, both the nuclear proteins and DNA (chromatin) of germ cells are modified, thus resulting in spermatozoa of functionally poorer quality. Our three specific aims are: First to determine what specific molecular changes occur in organelles of sperm (nuclear matrix/cytoplasmic droplet) during aging. Next, to assess how altered expression of glutathione peroxidase 4 affects the ability of sperm to withstand modifications of oxidative stress that occur during aging. Third, to use stem cell transplantation to determine how aging of spermatogonial stem cells affects their potential for proliferation and differentiation. Together these studies will provide a clear indication of how aging affects both germ cell chromatin and function.
Amount: CA$765,800
Funding type: research
Funder scheme: Operating Grant
Start date: 2008-10-01
End date: 2013-09-30
Investigator: Bernard Robaire
Institution: McGill University
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Funded outputs count: 6
Funder award ID: 89767_1
OpenAlex ID: G575593483