Biol Reprod. 2013 Nov 13. [Epub ahead of print]
Aging Results in Molecular Changes in an Enriched Population of Undifferentiated Rat Spermatogonia.
Abstract
There is a strong correlation between increasing paternal age and a decline in reproductive function. Testis aging is associated with testicular atrophy, increased DNA damage and de novo mutations. It is unclear whether these problems arise from the spermatogonial stem cells (SSCs), a build up of anomalies as older germ cells progress through spermatogenesis, or both. We hypothesize that with the continual divisions of SSCs that maintain the germ cell population, there is an alteration of these cells over time. To test this we utilized transgenic rats, at 4 (young), 18 and 21 mo (aged), that express GFP in germ cells only. We first examined the number and activity of SSCs from the different age groups by transplantation. Aged rats had numerically fewer SSCs than young rats (<50 21-mo-old="" a="" age="" also="" and="" any="" atrophy="" cd9="" cells="" changes="" class="s4" colony="" despite="" deteriorates.="" early="" evaluate="" in="" isolated="" lack="" length="" molecular="" not="" occurring="" of="" population="" quality="" rats="" reduction="" show="" significant="" span="" spermatogenesis="" ssc-enriched="" sscs="" suggesting="" testicular="" that="" the="" though="" to="" we="" with="">+
cells using FACS (confirmed by transplantation studies) and extracted RNA for microarray analysis. In the aged CD9+ cells, 60 transcripts were upregulated and over 500 were downregulated compared to the young. An altered expression was found for transcripts involved in mitosis and in DNA damage response. These results suggest that there are molecular alterations in the SSC-enriched population of CD9+ aged cells implying that reproductive aging originates in the undifferentiated cells of spermatogenesis.
KEYWORDS:
Aging, Gene expression, Spermatogonia, Spermatogonial stem cells, Testis
PMID: 24227752 [PubMed - as supplied by publisher]
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