Amniocytes from aneuploidy embryos have enhanced random aneuploidy and signs of senescence — Can these findings be related to medical problems?

• Individuals with aneuploidy tend to develop malignancies and earlier age related diseases.
• Amniocytes of autosomal aneuploidies possess enhanced random aneuploidy and senescence.
• Genomic instability is more pronounced in autosomal compared to sex chromosome aneuploidy.
• Partial inactivation of the extra X chromosome might have a protective effect.
• The genomic instability in amniocytes with aneuploidy might explain their increased morbidity.

ObjectivesGenomic aneuploidy is a common cause of human genetic disorders. Individuals with aneuploidy tend to develop malignancies. Recent studies correlated aneuploidy with early aging, senescence and organ dysfunction. This study investigated potential explanations for these increased risks by evaluating random aneuploidy and senescence rates in amniocytes from fetuses with aneuploidy.MethodsThe rates of random aneuploidy in amniocytes from normal pregnancies were evaluated and compared to amniocytes from fetuses with trisomies 21, 18 and 47,XXY using a FISH technique with X + Y, 9 and 18 probes. Senescence was evaluated by calculating the percentage of amniocytes with fragmented nuclei: senescence associated heterochromatin foci (SAHF), using DAPI staining.ResultsSignificantly increased rates of cells with aneuploidy were observed in trisomies 18 and 21, and 47,XXY (p < 0.001) compared to the control group for the somatic and sex chromosomes. Increased rates of amniocytes with SAHFs were observed among the trisomy samples compared to the control group.ConclusionsHigher incidence of random aneuploidy and senescence were observed in amniocytes from fetuses with trisomy. These findings might explain the greater lifetime tendency to develop malignancies and diseases related to early aging in these individuals.