Study of aneuploidy in normal and abnormal germ cells from semen of fertile and infertile men

Abstract

This study was undertaken with the aim of investigating the cytogenetic constitution of normal as well as abnormal spermatozoa and immature germ cells found in semen of normal men and infertile patients. A specific protocol of double in-situ hybridization for chromosomes 1 and 17 based on colorimetric detection of the hybridization signals (ISH) and brightfield microscopy analysis of cellular morphology was applied. Also the influence of paternal age on sperm aneuploidy was investigated. We found that, at least in the age range analysed (28-54 years) and for semen of good quality (total normal motile counts above 10 x 10(6)) (n = 17), paternal age has no influence on baseline rates of sperm aneuploidy. However, with decreasing semen quality (total normal motile sperm counts below 5 x 10(6)) (n = 6) significantly higher rates of sperm aneuploidy for autosomes 1 and 17 were scored (0.8 versus 1.43%) (P < 0.001). Regardless of the type of semen analysed, a number of morphologically abnormal spermatozoa were found to be hyperhaploid or diploid in a high percentage of cases (20 and 10% respectively). The same was found for immature germ cells (aneuploidy rate of 18%). We conclude that in infertile men with poor quality semen a direct relationship may exist between the impairment of the spermatogenesis process (as reflected by an increased production of morphologically and cytogenetically abnormal germ cells) and rates of baseline aneuploidy occurring in normal spermatozoa. Infertile couples undergoing assisted reproduction treatment need to be counselled about the risk of using spermatozoa which may carry higher rates of non-disjunction for different chromosomes. While sperm hyper- or hypohaploidy for some chromosomes (X,Y) implies counselling couples about the risk of abnormal phenotype in their offspring, most autosomal sperm aneuploidies probably translate only into lower rates of embryo fertilization and survival.

DNA Fragmentation, Mitochondrial Dysfunction and Chromosomal Aneuploidy in the Spermatozoa of Oligoasthenoteratozoospermic Males

“…Semen from infertile men has been found to contain a greater percentage of spermatozoa with fragmented DNA than semen from fertile men (27,28). On the chromosome level, aneuploidy has been documented as a causal factor of male infertility (17,18,(20)(21)(22)(23). On the cellular level, mitochondrial function has been reported to associate with reproductive performance, both in males and in females.…”

“…Chromosomal abnormalities have been extensively found in the spermatozoa of many infertile men (17)(18)(19)(20)(21). The incidence of chromosomal structural aberrations increases among patients undergoing ICSI programs than those on IVF programs (20,21).…”

Case reports to suggest an algorithm for management of total fertilisation failure prior to use of donor gametes

“…Following the exclusion of obvious factors that would dictate gamete donation as first-line treatment, focus should initially be on investigation. Although genetic markers of sperm have not necessarily been related to TFF, both increased sperm DNA fragmentation [14] and sperm aneuploidy levels [15] have been demonstrated to impact negatively on fertilisation rates. Furthermore, a correlation between increased sperm DNA fragmentation and loss PLCζ activity has also been suggested [16].…”

Polyflagellated macrocephalic spermatozoa: failure factor in IVF/ICSI

“…For some authors such as Guttenbach and Miharu, there is no difference in the proportion of aneuploidy between fertile and infertile men; for the others, on the contrary, higher rates of aneuploidy are observed in infertile males with normal somatic karyotyping. [3][4][5][6][7][8][9] Some authors report a correlation between sperm quality and proportion of aneuploidy. 7,8,[10][11][12] Indeed, according to them, there is a relationship between aneuploidy and the concentration of spermatozoa and, on the other hand, between aneuploidy and the mobility of spermatozoa.…”