Aneuploidy Induction in Germ Cell Systems

Aneuploidy, the gain or loss of whole chromosomes, is a critical source of reproductive failure, congenital disorders and tumourigenesis. In germ cell systems, errors in meiotic chromosome segregation arise from defects in crossover formation, kinetochore–spindle attachments and checkpoint signalling. Physical agents such as ionising radiation and heat, chemical aneugens that target microtubule dynamics, and genotypic factors including point mutations or chromosomal rearrangements all contribute to nondisjunction. Germ cells of model organisms—from yeast and Drosophila to mice and human spermatozoa—have revealed conserved mechanisms by which spindle disruption, reduced chiasma frequency and cohesion fatigue lead to the formation of univalents and lagging chromosomes. Advances in cytogenetic assays, fluorescence in situ hybridisation and high-throughput sperm aneuploidy screening have refined our ability to detect low-frequency events. Understanding how environmental agents and therapeutic drugs induce aneuploidy in germ cells informs risk assessment for fertility, guides safer drug design and improves our knowledge of transgenerational genetic stability.

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Recent work in a mammalian model has demonstrated that the chemotherapeutic agent epirubicin not only breaks DNA but also acts as an aneugen in male germ cells. By combining BrdU incorporation to monitor meiotic progression with centromere-specific probes, researchers showed a 48-hour delay in meiosis and significant increases in disomic sperm for chromosomes X, Y and autosome 8. Notably, a bias towards XX and YY sperm implies missegregation at the second meiotic division, highlighting drug-induced spindle malfunction as a source of aneuploid gametes.

Foundational genetic analyses in Drosophila melanogaster females have elucidated how reduced crossover frequency and distributive pairing influence nondisjunction. Early studies demonstrated that inversion heterozygosity, radiation and heat shock generate univalent chromosomes that fail to align correctly on the metaphase plate. These univalents, when of compatible size, may undergo nonhomologous pairing, leading to mis-oriented segregation and resultant aneuploid oocytes.

Methodological advances in direct human gamete assessment have been exemplified by fluorescent staining of sex chromosomes in sperm. A key study employed quinacrine dihydrochloride staining to quantify Y chromosome disomy in ejaculated spermatozoa. This approach bypasses invasive sampling, enabling rapid evaluation of occupational or therapeutic exposures as a predictor for broader autosomal missegregation. Such non-invasive screening is now considered a valuable barometer for assessing reproductive risk in exposed populations.

Aneuploidy Induction in Germ Cell Systems publication trend

The graph below shows the total number of articles in aneuploidy induction in germ cell systems across all publications each year (not limited to Nature Index journals).

Technical terms

Aneuploidy: The state of having a chromosome number that is not an exact multiple of the haploid complement.

Germ cell: A reproductive cell (sperm or oocyte) that undergoes meiosis to produce gametes.

Nondisjunction: Failure of homologous chromosomes or sister chromatids to separate properly during cell division.

Aneugen: An agent that induces aneuploidy by disrupting the mitotic or meiotic spindle apparatus without necessarily causing DNA breaks.

Micronucleus: A small extranuclear body containing one or more whole chromosomes or chromosomal fragments, indicative of genomic instability.

References

1. Aneugenic Effects of Epirubicin in Somatic and Germinal Cells of Male Mice. PLOS ONE (2014).
2. Origin of meiotic nondisjunction in Drosophila females.. Environmental Health Perspectives (1979).
3. Mechanisms of nondisjunction induction in drosophila oocytes.. Environmental Health Perspectives (1979).
4. Detection of aneuploidy in human sperm.. Environmental Health Perspectives (1979).