Aneuploidy in human spermatozoa.

Area of Science:

• Reproductive biology
• Human genetics
• Cytogenetics

Background:

• Disomy, the presence of an extra chromosome, can occur in sperm and lead to aneuploid offspring.
• Understanding the frequency and distribution of sperm disomy is crucial for assessing reproductive risks.
• Previous studies have investigated sperm disomy in various populations, but comprehensive analysis is needed.

Purpose of the Study:

• To review and analyze the frequency and distribution of disomy in spermatozoa across different male populations.
• To compare sperm disomy rates in healthy men, fathers of aneuploid offspring, and individuals with sex chromosome abnormalities.
• To evaluate the potential link between elevated sperm disomy and the risk of paternally derived aneuploid pregnancies.

Main Methods:

• Multicolor fluorescence in situ hybridization (FISH) analysis was performed on decondensed sperm nuclei.
• Sperm samples were obtained from healthy men, fathers of aneuploid offspring, and males with Klinefelter syndrome (47,XXY) and XYY syndrome (47,XYY).
• Frequencies of autosomal and sex chromosome disomy were quantified and compared across groups.

Main Results:

• In healthy men, autosomal disomy is approximately 0.1%, with variations across chromosomes (e.g., 0.03% for chromosome 8 to 0.47% for chromosome 22).
• Chromosomes 21 and sex chromosomes show significantly elevated disomy frequencies in many studies (0.18% and 0.27%, respectively).
• Total disomy in FISH studies was 2.26%, estimating aneuploidy at 4.5%, which is higher than sperm karyotype findings (1.8%).
• Increased disomy levels were observed in some normal men ('stable variants') and men fathering children with Down, Turner, and Klinefelter syndromes.
• Males with Klinefelter (47,XXY) and XYY (47,XYY) syndromes exhibit increased sex chromosome abnormalities, autosomal disomies, and diploid spermatozoa.
• Sex chromosome aneuploidy is more frequent than autosomal aneuploidy in controls, patients with sex chromosome abnormalities, and fathers of paternally derived Klinefelter, Turner, and Down syndromes.

Conclusions:

• Men with moderately elevated sperm aneuploidy rates may face a higher risk of fathering paternally derived aneuploid pregnancies.
• Lifestyle factors like smoking, alcohol, and caffeine consumption require further investigation for their combined effects on sperm aneuploidy.
• Sex chromosome aneuploidy is a prominent feature in individuals with sex chromosome abnormalities and their offspring, highlighting the importance of cytogenetic analysis.