How do chromosomal abnormalities affect embryo quality?
I. Definition and classification of chromosomal abnormalities: the crisis of “genetic code” of embryo development Chromosomal abnormality refers to abnormal changes in the number or structure of chromosomes, which is one of the core factors leading to embryonic development failure, birth defects and genetic diseases. Human cells contain 23 pairs of chromosomes (22 pairs of autosomes + 1 pair of sex chromosomes), and an imbalance in any one pair of chromosomes can lead to catastrophic consequences. Aneuploidy:Trisomy (e.g. trisomy of chromosome 21 → Down syndrome, trisomy 18 → Edwards syndrome)Monosomal syndromes (e.g., X chromosome monosomy → Turner syndrome)Polyploidy: e.g. triploidy (69 chromosomes), embryos usually do not survive to mid-gestation. Deletions (e.g. 5p deletion → cat-call syndrome)Duplications (e.g. 16p11.2 duplication → increased risk of autism)Translocations (carriers of balanced translocations may have chromosomally abnormal offspring)Inversions (e.g., chromosome 9 inter-arm inversion may trigger recurrent miscarriages) Ⅱ.The 5 major mechanisms by which chromosomal abnormalities affect embryo quality About 50%-70% of early spontaneous abortions are directly related to chromosomal abnormalities in embryos. Abnormal chromosome combinations interfere with the following key processes: Zygote genome activation (ZGA): on day 3 after fertilization, the embryo initiates its own gene expression, and the chromosomal abnormality results in the silencing of key genes (e.g., OCT4, NANOG).Uncontrolled cell division: aneuploidy triggers failure of the spindle checkpoint (SAC), leading to multipolar division or division arrest. Clinical data: Only 20% of trisomy 21 embryos develop to the blastocyst stage;Less than 5% of trisomy 16 embryos reach the blastocyst stage. Chromosomal abnormalities cause organ malformations by disrupting the HOX gene cluster (which regulates axial body development) and the WNT signaling pathway (which controls cell fate): Heart defects: atrial septal defects are present in 40%-60% of children with trisomy 21;Neurological abnormalities: failure of neural tube closure in up to 80% of trisomy 18 embryos. Placenta-specific…
