DNA organization in human spermatozoa

Division of Urology, Robert Wood Johnson University Medical School, New Brunswick, New Jersey 08903-0019.
Journal of Andrology (Impact Factor: 1.69). 03/1994; 15(2):139-44. DOI: 10.1002/j.1939-4640.1994.tb00419.x
Source: PubMed

ABSTRACT Previous studies from this laboratory on hamster spermatozoa have demonstrated that rodent sperm DNA is packaged into the sperm nucleus in a specific manner by nuclear structures. The entire genome is organized into DNA loop domains attached at their bases to a sperm nuclear matrix, the skeletal structure of the nucleus. When nuclei are completely decondensed, the nuclear matrix dissipates, and the entire genome remains anchored to a single structure located at the base of the tail, termed the nuclear annulus. Here, we have extended these studies to human sperm nuclei, which were found to be similar to hamster. Human sperm DNA was found to be organized into loop domains attached at their bases to a nuclear matrix. The average size of the human sperm halo of DNA surrounding the extracted sperm nucleus (made up of DNA loop domains) was about 50% smaller than those that have been reported for somatic cells (this corresponds to an approximate loop domain size of 26.8 +/- 2.1 kb). Human sperm DNA also remained anchored to the base of the tail when completely decondensed, indicating the existence of a nuclear annulus-like structure in human spermatozoa; but, unlike the hamster nuclear annulus, the human annulus could not be isolated because of its structural instability when separated from the tail. Using human centromere repeats as a probe for in situ hybridization, we examined the packaging of individual DNA sequences within the sperm nucleus. These studies demonstrate that human sperm DNA is highly organized by nuclear structures.

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Available from: W. Steven Ward, Oct 13, 2014
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    • "These processes are associated with marked changes in the structure of the sperm chromatin (D'Occhio et al., 2007). As spermatogenesis proceeds, 85% of the histone nucleoproteins are replaced by transition proteins, which are subsequently replaced by small, arginine-rich proteins known as protamines (Oliva and Dixon, 1990; Barone et al., 1994; Balhorn et al., 2000). These changes give a compact, denaturating-resistant structure to the chromatin. "
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    ABSTRACT: Seminal proteins can be considered as factors that control fertilization. Clusterin is one such protein that has been implicated in many activities, including apoptosis inhibition, cell cycle control, DNA repair, and sperm maturation. In this study, the relationship between human secretory clusterin in seminal plasma with sperm parameters, protamine deficiency, and DNA fragmentation was investigated. Semen samples were collected from 63 Iranian men and semen analysis was performed according to World Health Organization criteria and Computer Aided Semen Analysis (CASA). The concentration of secretory clusterin (sCLU) in seminal plasma was measured by enzyme-linked immunosorbant assay (ELISA), protamine deficiency was determined by chromomycin A3 staining, and sperm DNA fragmentation was checked by sperm chromatin dispersion. The level of sCLU in seminal fluid of fertile patients was 48.3 ± 38.6 ng/ml and in infertile patients was 15.5 ± 9.7 ng/ml, and the difference was significant (p < 0.001). sCLU was correlated negatively with protamine deficiency, sperm DNA fragmentation, and abnormal morphology. In conclusion, seminal clusterin can be considered a marker for quick assessment of semen quality in male infertility studies. Mol. Reprod. Dev. © 2013 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 06/2013; DOI:10.1002/mrd.22202 · 2.68 Impact Factor
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    • "The chromatin structure of mammalian sperm nuclei differs significantly from that of somatic cells (Barone et al. 1994; Churikov et al. 2004; Steger et al. 1998). In the course of spermiogenesis, the extremely compact chromatin structure of mature spermatozoa (Poccia 1986) is formed by the replacement of histones by the transition proteins TP1 and TP2, which themselves are in turn replaced by protamines (Steger et al. 1998; Wouters-Tyrou et al. 1998). "
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    ABSTRACT: In spermiogenesis, spermatid differentiation is marked by dramatic changes in chromatin density and composition. The extreme condensation of the spermatid nucleus is characterized by an exchange of histones to transition proteins and then to protamines as the major nuclear proteins. Alterations in DNA topology that occur in this process have been shown to require the controlled formation of DNA strand breaks. Poly(ADP-ribosyl)ation is a posttranslational modification of proteins mediated by a family of poly(ADP-ribose) polymerase (PARP) proteins, and two family members, PARP-1 and PARP-2, are activated by DNA strand breaks that are directly detected by the DNA-binding domains of these enzymes. Here, we show for the first time that poly(ADP-ribose) formation, mediated by poly(ADP-ribose) polymerases (PARP-1 and presumably PARP-2), occurs in spermatids of steps 11-14, steps that immediately precede the most pronounced phase of chromatin condensation in spermiogenesis. High levels of ADP-ribose polymer were observed in spermatid steps 12-13 in which the highest rates of chromatin nucleoprotein exchanges take place. We also detected gamma-H2AX, indicating the presence of DNA double-strand breaks during the same steps. Thus, we hypothesize that transient ADP-ribose polymer formation may facilitate DNA strand break management during the chromatin remodeling steps of sperm cell maturation.
    Chromosoma 06/2005; 114(1):67-74. DOI:10.1007/s00412-005-0344-6 · 3.26 Impact Factor
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    • "When the human sperm undergoes decondensation, the DNA remains anchored to the base of the tail. This fact suggests the presence of a nuclear annulus-like structure in human sperm (Barone et al., 1994). This DNA organization not only permits the very tightly packaged genetic information to be transferred to the egg, but also ensures that the DNA is delivered in a physical and chemical form that allows the developing embryo to access the genetic information (Sakkas et al., 1999a). "
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    ABSTRACT: Sperm DNA integrity is essential for the accurate transmission of genetic information. It has a highly compact and complex structure and is capable of decondensation-features that must be present in order for a spermatozoon to be considered fertile. Any form of sperm chromatin abnormalities or DNA damage may result in male infertility. In support of this conclusion, it was reported that in-vivo fecundity decreases progressively when > 30% of the spermatozoa are identified as having DNA damage. Several methods are used to assess sperm chromatin/DNA, which is considered an independent measure of sperm quality that may yield better diagnostic and prognostic approaches than standard sperm parameters (concentration, motility and morphology). The clinical significance of this assessment lies in its association not only with natural conception rates, but also with assisted reproduction success rates. Also, it has a serious impact on the offspring and is highly prognostic in the assessment of fertility in cancer patients. Therefore, screening for sperm DNA damage may provide useful information in cases of male idiopathic infertility and in those men pursuing assisted reproduction. Treatment should include methods for prevention of sperm DNA damage.
    Human Reproduction Update 07/2003; 9(4):331-45. DOI:10.1093/humupd/dmg027 · 8.66 Impact Factor
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