Developmental tolerance and disease implications of aneuploidy

Area of Science:

• Genetics and Developmental Biology
• Cell Biology

Background:

• Aneuploidy, an abnormal chromosome number, is detrimental to cellular and organismal health and a primary cause of human miscarriages.
• Recent findings indicate a high prevalence of aneuploidy in early human embryos, stemming from both aneuploid gametes (especially from aged oocytes) and post-zygotic segregation errors leading to mosaicism.
• Interestingly, some aneuploid mosaic embryos can develop into healthy individuals.

Purpose of the Study:

• To review the compatibility of aneuploidy with normal embryo development.
• To explore the presence and implications of aneuploidy in somatic tissues, aging, and tumorigenesis.
• To emphasize the differential roles of various aneuploidy types (trisomies, monosomies, whole-chromosome, segmental) and the role of cell competition.

Main Methods:

• Literature review and synthesis of existing research on aneuploidy.
• Analysis of data on aneuploidy prevalence in gametes, early embryos, and somatic tissues.
• Discussion of mechanisms such as cell competition in managing aneuploidy.

Main Results:

• Aneuploidy is a frequent occurrence in early human embryos, contributing to developmental issues and miscarriages.
• Mosaic aneuploidy, arising from early cell divisions, is widespread and can paradoxically lead to viable offspring.
• Aneuploidy is also present in normal somatic tissues and is implicated in aging and cancer development.

Conclusions:

• Aneuploidy's impact varies significantly depending on its type and the developmental context.
• Cell competition is a key mechanism for tissues to manage the presence of aneuploid cells.
• Understanding aneuploidy is crucial for reproductive health, aging research, and cancer biology.