Selfish spermatogonial selection: evidence from an immunohistochemical screen in testes of elderly men

摘要: The dominant congenital disorders Apert syndrome, achondroplasia and multiple endocrine neoplasia–caused by specific missense mutations in the FGFR2, FGFR3 RET proteins respectively–represent classical examples of paternal age-effect mutation, a class that arises at particularly high frequencies sperm older men. Previous analyses DNA from randomly selected cadaveric testes showed levels corresponding exhibit very uneven spatial distributions, with localised hotspots surrounded large mutation-negative areas. These studies imply normal are mosaic for clusters mutant cells: these predicted to have altered growth signalling properties leading their clonal expansion (selfish spermatogonial selection), but extraction eliminates possibility study such processes tissue level. Using panel antibodies optimised detection spermatocytic seminoma, rare tumour origin, we demonstrate putative events frequent within elderly men (mean age: 73.3 yrs) can be classed into two broad categories. We found numerous small (less than 200 cells) cellular aggregations distinct immunohistochemical characteristics, portion seminiferous tubule, which uncertain significance. However more infrequently identified additional regions where entire tubules had circumferentially appearance extended through serial sections were physically contiguous (up 1 mm length), exhibited enhanced staining both marker downstream signal activation, pAKT. findings support concept populations spermatogonia individual mosaics regard thus fulfilling one predictions selfish selection.