X chromosome aneuploidy and micronuclei in fertile mares

Abstract Abnormalities of chromosomes are an important and well documented cause of disorders of sexual development, fertility problems and congenital anomalies in mammals. Detection of low-level 63,X/64,XX mosaicism during routine cytogenetic evaluation is a challenge because its clinical significance is not yet fully clear. This study describes the prevalence and levels of 63,X mosaicism for a cohort of fertile mares and compares the results with eight problem mares for which no clinical cause of sub-fertility was found. The study design allowed for the analysis of micronuclei which are biomarkers of genomic instability and can disturb cell divisions, drive cancer development or cause congenital diseases. Although 27% of the fertile mares were identified to be 63,X mosaics, the results showed that the rates of abnormal cells were very low (1-3%). Levels of abnormal cells in problem mares with 63,X mosaicism were similar or higher. The average rate of micronuclei in the blood of the fertile mares was ∼ 1%, well below the baseline (5%) which was proposed for peripheral blood of normal healthy humans. We found weak to modest, but not significant, correlations between the age of fertile mares and 63,X cells (Kendall’s tau b = 0.2905; p > 0.05) as well as the rate of micronuclei (Kendall’s tau b = 0.1896; p > 0.05). Likewise, the correlation between presence of a 63,X cell line and micronuclei rate was not significant (Kendall’s tau b = 0.3201; p > 0.05). The presence of 63,X cells in rates greater than 3% may indeed indicate a higher risk for sub-fertility and eventually for associated health problems in such mares. Detection and elimination of mares with high level of X aneuploidies from breeding may have a positive effect on the fertility within the general horse population. This data may support the evaluation of problem mares with mosaic karyotypes involving the X chromosome.