Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm.

This study compares the relative effects of advancing male age on multiple genomic defects in human sperm [DNA fragmentation index (DFI), chromatin integrity, gene mutations, and numerical chromosomal abnormalities], characterizes the relationships among these defects and with semen quality, and estimates the incidence of susceptible individuals for a well characterized nonclinical nonsmoking group of 97 men (22-80 years). Adjusting for confounders, we found major associations between age and the frequencies of sperm with DFI and fibroblast growth factor receptor 3 gene (FGFR3) mutations associated with achondroplasia (P < 0.01) with no evidence for age thresholds. However, we found no associations between age and the frequencies of sperm with immature chromatin, aneuploidies/diploidies, FGFR2 mutations (Apert syndrome), or sex ratio in this cohort. There were also no consistent correlations among genomic and semen-quality endpoints, except between DFI and sperm motility (r = -0.65, P < 0.001). These findings suggest there are multiple spermatogenic targets for genomically defective sperm with substantially variable susceptibilities to age. Our findings predict that as healthy males age, they have decreased pregnancy success with trends beginning in their early reproductive years, increased risk for producing offspring with achondroplasia mutations, and risk of fathering offspring with Apert syndrome that may vary across cohorts, but with no increased risk for fathering aneuploid offspring (Down, Klinefelter, Turner, triple X, and XYY syndromes) or triploid embryos. Our findings also suggest that the burden of genomic damage in sperm cannot be inferred from semen quality, and that a small fraction of men are at increased risk for transmitting multiple genetic and chromosomal defects.

Molecular phylogenetics of the Peromyscus boylii species group (Rodentia: muridae) based on mitochondrial cytochrome b sequences.

Variation in the mitochondrial cytochrome b gene (1143 bp) was examined to estimate the phylogenetic relationships of taxa within the Peromyscus boylii species group. In addition, phylogenetic relationships among the aztecus, boylii, and truei species groups were addressed. Maximum-likelihood, neighbor-joining, and maximum-parsimony (weighted and equally weighted) analyses produced similar topologies with P. boylii, P. beatae, P. simulus, P. stephani, P. madrensis, P. levipes, and three undescribed taxa from western Mexico forming a monophyletic unit. At least two of the undescribed taxa from western Mexico potentially represent species. Members of the P. aztecus species group formed a clade separate from the P. boylii group and should be recognized as a distinct species group. P. sagax, P. polius, and P. pectoralis, formerly placed in the P. boylii species group, generally formed an unresolved polytomy with the P. truei, P. aztecus, and P. boylii species groups. P. attwateri formed a sister taxon relationship with members of the P. truei species group (P. difficilis and P. nasutus) and should be considered a member of this group. Members of the P. truei species group did not form a monophyletic unit, indicating that this species group is not monophyletic and may be composed of two assemblages.