Next Generation Sequencing Detects Premeiotic Errors in Human Oocytes

Area of Science:

• Reproductive Biology
• Human Genetics
• Developmental Biology

Background:

• Autosomal aneuploidy is a primary cause of human embryonic and fetal mortality.
• Errors during oogenesis (meiosis I or II) are the main contributors.
• Germinal mosaicism, leading to premeiotic aneuploidy, is an underrecognized factor.

Purpose of the Study:

• To independently investigate the incidence of premeiotic aneuploidy in unmanipulated human oocytes.
• To validate findings from previous molecular cytogenetic studies.
• To assess the impact of premeiotic aneuploidy on oocyte euploidy.

Main Methods:

• Utilized next-generation sequencing (NGS) for analysis.
• Examined a series of 140 unselected oocytes from 42 women.
• Analyzed both immature (germinal vesicle, metaphase I) and mature (metaphase II) oocytes.

Main Results:

• Confirmed premeiotic aneuploidy incidence exceeding 10% (11.4% in this study).
• Identified 16 out of 140 oocytes (11.4%) with premeiotic aneuploidy.
• Found higher aneuploidy rates in mature oocytes (21.4%) compared to immature ones (8.93%).
• Observed both simple and complex chromosomal errors in aneuploid oocytes.

Conclusions:

• Germinal mosaicism leading to premeiotic aneuploidy is a consistent finding in at least 10% of oocytes.
• Premeiotic aneuploidy significantly elevates the risk of producing an aneuploid mature oocyte.
• This finding may explain aneuploid conceptions in younger women, independent of maternal age.