Chromosome (re)positioning in spermatozoa of fathers and sons – carriers of reciprocal chromosome translocation (RCT)

Abstract

BackgroundNon-random chromosome positioning has been observed in the nuclei of several different tissue types, including human spermatozoa. The nuclear arrangement of chromosomes can be altered in men with decreased semen parameters or increased DNA fragmentation and in males with chromosomal numerical or structural aberrations. An aim of this study was to determine whether and how the positioning of nine chromosome centromeres was (re)arranged in the spermatozoa of fathers and sons – carriers of the same reciprocal chromosome translocation (RCT).MethodsFluorescence in situ hybridization (FISH) was applied to analyse the positioning of sperm chromosomes in a group of 13 carriers of 11 RCTs, including two familial RCT cases: t(4;5) and t(7;10), followed by analysis of eight control individuals. Additionally, sperm chromatin integrity was evaluated using TUNEL and Aniline Blue techniques.ResultsIn the analysed familial RCT cases, repositioning of the chromosomes occurred in a similar way when compared to the data generated in healthy controls, even if some differences between father and son were further observed. These differences might have arisen from various statuses of sperm chromatin disintegration.ConclusionsNuclear topology appears as another aspect of epigenetic genomic regulation that may influence DNA functioning. We have re-documented that chromosomal positioning is defined in control males and that a particular RCT is reflected in the individual pattern of chromosomal topology. The present study examining the collected RCT group, including two familial cases, additionally showed that chromosomal factors (karyotype and hyperhaploidy) have superior effects, strongly influencing the chromosomal topology, when confronted with sperm chromatin integrity components (DNA fragmentation or chromatin deprotamination).Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0470-7) contains supplementary material, which is available to authorized users.

How much, if anything, do we know about sperm chromosomes of Robertsonian translocation carriers?

“…Since we do not know what mechanisms are responsible for the fact that a given RobT does not always affect male fertility, it would be undoubtedly interesting to collect analogous data on fertile RobT carriers, especially in family scenarios. However, we know from our own experience that the potential for such unique sample collection is very limited [121,122].…”

Human live spermatozoa morphology assessment using digital holographic microscopy

“…Investigations of infertile men with small supernumerary marker chromosomes (sSMCs) reveal that the chromosome topology in the sperm nuclear territory may lead to infertility 27 . Individual patterns of chromosomal topology may be the result of reciprocal chromosomal translocation 28 . We can only speculate that certain differences in chromosome topology may influence sperm 3-D morphology.…”

Familial Infertility (Azoospermia and Cryptozoospermia) in Two Brothers—Carriers of t(1;7) Complex Chromosomal Rearrangement (CCR): Molecular Cytogenetic Analysis

“…Such rebuilding and rearrangement, leading to simpler or more complicated aberrations, arises in approximately 45% of CCR cases [17]. An example is a case of a fertile CCR carrier of der(Y;15),rob (13;14) who inherited his CCR from both parents: der(Y) form his father and rob (13;14) from his mother, and fathered by himself a healthy daughter (46,XX) [36]. In the rest of the CCR cases, the rearrangement remained the same (also as described in our study).…”

“…Likely, the accumulation of two rearrangements simultaneously, followed by the increased frequency of genetically unbalanced spermatozoa, resulted in a lack of conception. Similarly, in RCT carriers, there are also known cases of varied fertility statuses in male family members [38][39][40][41][42][43][44][45][46]. The reasons for such situation remain unclear.…”