The origin of abnormalities in recurrent aneuploidy/polyploidy

Area of Science:

• Genetics
• Reproductive Biology
• Cytogenetics

Background:

• Recurrent miscarriage (RM) can stem from sporadic chromosomal abnormalities, particularly trisomy, with increasing maternal age.
• Alternative explanations for RM include gonadal mosaicism, chromosomal structural issues, sperm aneuploidy, or ovarian aging.
• Investigating couples with multiple aneuploid spontaneous abortions (SAs) is crucial for understanding RM etiology.

Purpose of the Study:

• To investigate the cytogenetic and molecular basis of recurrent aneuploid/polyploid spontaneous abortions (SAs) in couples with a history of two or more such events.
• To determine the frequency of gonadal mosaicism as a cause for recurrent aneuploid SAs.
• To identify the parental origin of chromosomal abnormalities in recurrent SAs.

Main Methods:

• Cytogenetic and molecular analysis of 122 spontaneous abortions (SAs) from 54 couples with documented recurrent aneuploid/polyploid SAs.
• Comparison of abnormality distribution with a control group of 307 SAs without recurrent aneuploidy.
• Determination of the origin (maternal or paternal) of chromosomal abnormalities in a subset of SAs.

Main Results:

• The distribution of chromosomal abnormalities in couples with recurrent SAs was similar to that in sporadic cases.
• Recurrence of the exact same abnormality was observed in 8 families, a frequency consistent with chance, not gonadal mosaicism.
• Maternal meiotic errors were the predominant cause of trisomy (30/32) and triploidy (1/2), with paternal origin in 2 trisomies and 1 triploidy.

Conclusions:

• The primary cause of trisomy in recurrent spontaneous abortions is maternal meiotic error, strongly associated with increased maternal age.
• Gonadal mosaicism is an infrequent explanation for recurrent aneuploid spontaneous abortions.
• While maternal age is the dominant factor, some population variability in aneuploidy risk may exist.