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Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient.

Olszewska M, Wanowska E, Kishore A, Huleyuk N, Georgiadis AP, Yatsenko AN, Mikula M, Zastavna D, Wiland E, Kurpisz M - Sci Rep (2015)

Bottom Line: The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat.Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC.This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Genetics, Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, Strzeszynska 32, 60-479 Poznan, Poland.

ABSTRACT
Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC(+)) and spermatozoa with normal chromosome complement (sSMC(-)), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC(+) to sSMC(-) spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 - 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient's sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

No MeSH data available.


Related in: MedlinePlus

The confocal representation of the positioning of sSMC and chromosome 15 centromeres demonstrated in two geometrical perspectives obtained by confocal microscopy.Red: centromere-specific probe for chromosome 15; green: SMAD6 gene locus (15q22.31). Scale bar: 3.0 μm. (a) Spermatozoa bearing sSMC (sSMC+) with two red and one green FISH signals. (b) Spermatozoa without sSMC (sSMC−) with one red and one green FISH signals.
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f3: The confocal representation of the positioning of sSMC and chromosome 15 centromeres demonstrated in two geometrical perspectives obtained by confocal microscopy.Red: centromere-specific probe for chromosome 15; green: SMAD6 gene locus (15q22.31). Scale bar: 3.0 μm. (a) Spermatozoa bearing sSMC (sSMC+) with two red and one green FISH signals. (b) Spermatozoa without sSMC (sSMC−) with one red and one green FISH signals.

Mentions: The positioning results for the sSMC and chromosome 15 centromere using confocal analysis (3D) corresponded with the radial results. Representative imagery from confocal microscopy are presented in Fig. 3 and the Supplementary files, which contain animations of spermatozoa with and without sSMC (see Supplementary Videos S4 and S5 online). There was a statistically significant difference (P < 0.0001) in the frequencies of centromere 15’s localization in particular areas between the sSMC+ and sSMC− spermatozoa. In the sSMC+ sperm, the nucleus of almost all (92.5%) of the centromeres of chromosome 15 were localized centrally (shell no. 1 ‘cen’), followed by a small frequency in shell no. 2 (‘int’ 7.5%), and a lack of signals in a shell no. 3 (‘per’ 0%) (counted according to description in ‘Materials and Methods’). In the sSMC− spermatozoa, the highest frequency of chromosome 15 centromeres (87.5%) was noted for the ‘int’ shell no. 2, while for the remaining shells, the frequencies were lower (no. 1 ‘cen’ 12.5%; no. 3 ‘per’ 0%). sSMC strongly preferred the intermediate ‘int’ position (shell no. 2, 97.5%) (shell no. 1 ‘cen’ 2.5%; no. 3 ‘per’ 0%).


Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient.

Olszewska M, Wanowska E, Kishore A, Huleyuk N, Georgiadis AP, Yatsenko AN, Mikula M, Zastavna D, Wiland E, Kurpisz M - Sci Rep (2015)

The confocal representation of the positioning of sSMC and chromosome 15 centromeres demonstrated in two geometrical perspectives obtained by confocal microscopy.Red: centromere-specific probe for chromosome 15; green: SMAD6 gene locus (15q22.31). Scale bar: 3.0 μm. (a) Spermatozoa bearing sSMC (sSMC+) with two red and one green FISH signals. (b) Spermatozoa without sSMC (sSMC−) with one red and one green FISH signals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663790&req=5

f3: The confocal representation of the positioning of sSMC and chromosome 15 centromeres demonstrated in two geometrical perspectives obtained by confocal microscopy.Red: centromere-specific probe for chromosome 15; green: SMAD6 gene locus (15q22.31). Scale bar: 3.0 μm. (a) Spermatozoa bearing sSMC (sSMC+) with two red and one green FISH signals. (b) Spermatozoa without sSMC (sSMC−) with one red and one green FISH signals.
Mentions: The positioning results for the sSMC and chromosome 15 centromere using confocal analysis (3D) corresponded with the radial results. Representative imagery from confocal microscopy are presented in Fig. 3 and the Supplementary files, which contain animations of spermatozoa with and without sSMC (see Supplementary Videos S4 and S5 online). There was a statistically significant difference (P < 0.0001) in the frequencies of centromere 15’s localization in particular areas between the sSMC+ and sSMC− spermatozoa. In the sSMC+ sperm, the nucleus of almost all (92.5%) of the centromeres of chromosome 15 were localized centrally (shell no. 1 ‘cen’), followed by a small frequency in shell no. 2 (‘int’ 7.5%), and a lack of signals in a shell no. 3 (‘per’ 0%) (counted according to description in ‘Materials and Methods’). In the sSMC− spermatozoa, the highest frequency of chromosome 15 centromeres (87.5%) was noted for the ‘int’ shell no. 2, while for the remaining shells, the frequencies were lower (no. 1 ‘cen’ 12.5%; no. 3 ‘per’ 0%). sSMC strongly preferred the intermediate ‘int’ position (shell no. 2, 97.5%) (shell no. 1 ‘cen’ 2.5%; no. 3 ‘per’ 0%).

Bottom Line: The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat.Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC.This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

View Article: PubMed Central - PubMed

Affiliation: Institute of Human Genetics, Polish Academy of Sciences, Department of Reproductive Biology and Stem Cells, Strzeszynska 32, 60-479 Poznan, Poland.

ABSTRACT
Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC(+)) and spermatozoa with normal chromosome complement (sSMC(-)), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC(+) to sSMC(-) spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 - 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient's sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

No MeSH data available.


Related in: MedlinePlus