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Hierarchical radial and polar organisation of chromosomes in human sperm

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Abstract

It is well established that chromosomes occupy distinct positions within the interphase nuclei, conferring a potential functional implication to the genome. In addition, alterations in the nuclear organisation patterns have been associated with disease phenotypes (e.g. cancer or laminopathies). The human sperm is the smallest cell in the body with specific DNA packaging and the mission of delivering the paternal genome to the oocyte during fertilisation. Studies of nuclear organisation in the sperm have postulated nonrandom chromosome position and have proposed a chromocentre model with the centromeres facing toward the interior and the telomeres toward the periphery of the nucleus. Most studies have assessed the nuclear address in the sperm longitudinally predominantly using centromeric or telomeric probes and to a lesser extent with whole chromosome paints. To date, studies investigating the radial organisation of human sperm have been limited. The purpose of this study was to utilise whole chromosome paints for six clinically important chromosomes (18, 19, 21, 22, X, and Y) to investigate nuclear address by assessing their radial and longitudinal nuclear organisation. A total of 10,800 sperm were analysed in nine normozoospermic individuals. The results have shown nonrandom chromosome position for all chromosomes using both methods of analysis. We present novel radial and polar analysis of chromosome territory localization within the human sperm nucleus. Specifically, a hierarchical organisation was observed radially with chromosomes organised from the interior to the periphery (chromosomes 22, 21, Y, X, 19, and 18 respectively) and polar organisation from the sperm head to tail (chromosomes X, 19, Y, 22, 21, and 18, respectively). We provide evidence of defined nuclear organisation in the human sperm and discuss the function of organisation and potential possible clinical ramifications of these results in regards to male infertility and early human development.

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Abbreviations

CTs:

Chromosome territories

DAPI:

4′,6-Diamidino-2-phenylindole

DNA:

Deoxyribonucleic acid

DTT:

Dithiothreitol

FISH:

Fluorescence in situ hybridization

HCl:

Hydrochloric acid

ICSI:

Intracytoplasmic sperm injection

NaCl:

Sodium chloride

PBS:

Phosphate-buffered Saline

Rpm:

Rotations per minute

SSC:

Saline sodium citrate

TRITC:

Tetramethyl rhodamine isothiocyanate

Tris:

2-Amino-2-hydroxymethyl-propane-1,3-diol

WCP:

Whole chromosome paint

2D:

Two dimensional

3D:

Three dimensional

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Acknowledgments

We would like to thank the following for their help in the success of this project: the patients who participated in this research study, IVF Florida Reproductive Associates staff, Michael Ellis (Digital Scientific UK), and Dr. Lakshmi Rao Kandukuri.

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Authors and Affiliations

  1. Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA

    N. M. Millan, P. Lau, M. Hann, D. Ioannou & H. G. Tempest

  2. IVF Florida Reproductive Associates, Margate, FL, USA

    D. Hoffman, M. Barrionuevo, W. Maxson & S. Ory

Authors
  1. N. M. Millan
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  2. P. Lau
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  3. M. Hann
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  4. D. Ioannou
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  5. D. Hoffman
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  6. M. Barrionuevo
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  7. W. Maxson
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  8. S. Ory
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  9. H. G. Tempest
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Corresponding author

Correspondence to H. G. Tempest.

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Responsible Editor: Conly Rieder.

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Millan, N.M., Lau, P., Hann, M. et al. Hierarchical radial and polar organisation of chromosomes in human sperm. Chromosome Res 20, 875–887 (2012). https://doi.org/10.1007/s10577-012-9323-y

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  • DOI: https://doi.org/10.1007/s10577-012-9323-y

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