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A model for the control of DNA integrity by the sperm nuclear matrix.

Gawecka JE, Ribas-Maynou J, Benet J, Ward WS - Asian J. Androl. (2015 Jul-Aug)

Bottom Line: The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization.This suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells.The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology; Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USA.

ABSTRACT
The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization. However, we have demonstrated that even in this compacted state, sperm chromatin is subject to degradation at open configurations associated with the nuclear matrix through a process we have termed sperm chromatin fragmentation (SCF). This suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells. The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote. When sperm that have damaged DNA are injected into the oocyte, the newly created zygote responds by delaying DNA synthesis in the male pronucleus and, if the damage is severe enough, arresting the embryo's development. Here we present a model for paternal DNA regulation by the nuclear matrix that begins during sperm maturation and continues through early embryonic development.

No MeSH data available.


Related in: MedlinePlus

SCF in Epididymal and Vas Deferens Spermatozoa. These data were previously published in Yamauchi, et al.16 Spermatozoa from the epididymis (lanes 1–7) or the vas deferens (lanes 8–14) were embedded in agarose plugs, and incubated in mHCZB (modified Hepes-CZB, CZB medium buffered with HEPES) supplemented with MnCl2 and CaCl2 as described,16 for the times indicated, and treated with or without EDTA to reverse TOP2B-induced breaks. The plugs were then electrophoresed by FIGE.
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Figure 1: SCF in Epididymal and Vas Deferens Spermatozoa. These data were previously published in Yamauchi, et al.16 Spermatozoa from the epididymis (lanes 1–7) or the vas deferens (lanes 8–14) were embedded in agarose plugs, and incubated in mHCZB (modified Hepes-CZB, CZB medium buffered with HEPES) supplemented with MnCl2 and CaCl2 as described,16 for the times indicated, and treated with or without EDTA to reverse TOP2B-induced breaks. The plugs were then electrophoresed by FIGE.

Mentions: When mammalian sperm are incubated with divalent cations, all of the chromatin is fragmented to about 25 kb, in a process we have termed sperm chromatin fragmentation (SCF) (Figure 1, lanes 2, 4 and 6).16 The remarkable aspect of SCF is that when epididymal sperm are stimulated to undergo SCF, subsequent treatment with EDTA appears to reverse most of the breaks (Figure 1, lanes 3, 5 and 7). This is reminiscent of the reversible topoisomerase II (Top2) - induced breaks that occur in somatic cells as the first step of DNA degradation during apoptosis.1117 Since Top2 is a nuclear matrix associated protein.71718 this first step of apoptotic DNA degradation occurs on the nuclear matrix, and results in the chromatin being digested to loop-sized fragments, about 50 kb in length. As apoptosis progresses, nucleases interact with Top2 to irreversibly continue the DNA degradation.1920 If SCF is allowed to progress further in epididymal sperm, a similar type of nonreversible degradation occurs.21 We also see this irreversible degradation in sperm cells as they progress through the reproductive tract. When vas deferens sperm are induced to undergo SCF, the degradation is more complete and cannot be reversed as completely (Figure 1, lanes 9, 11 and 13).


A model for the control of DNA integrity by the sperm nuclear matrix.

Gawecka JE, Ribas-Maynou J, Benet J, Ward WS - Asian J. Androl. (2015 Jul-Aug)

SCF in Epididymal and Vas Deferens Spermatozoa. These data were previously published in Yamauchi, et al.16 Spermatozoa from the epididymis (lanes 1–7) or the vas deferens (lanes 8–14) were embedded in agarose plugs, and incubated in mHCZB (modified Hepes-CZB, CZB medium buffered with HEPES) supplemented with MnCl2 and CaCl2 as described,16 for the times indicated, and treated with or without EDTA to reverse TOP2B-induced breaks. The plugs were then electrophoresed by FIGE.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492052&req=5

Figure 1: SCF in Epididymal and Vas Deferens Spermatozoa. These data were previously published in Yamauchi, et al.16 Spermatozoa from the epididymis (lanes 1–7) or the vas deferens (lanes 8–14) were embedded in agarose plugs, and incubated in mHCZB (modified Hepes-CZB, CZB medium buffered with HEPES) supplemented with MnCl2 and CaCl2 as described,16 for the times indicated, and treated with or without EDTA to reverse TOP2B-induced breaks. The plugs were then electrophoresed by FIGE.
Mentions: When mammalian sperm are incubated with divalent cations, all of the chromatin is fragmented to about 25 kb, in a process we have termed sperm chromatin fragmentation (SCF) (Figure 1, lanes 2, 4 and 6).16 The remarkable aspect of SCF is that when epididymal sperm are stimulated to undergo SCF, subsequent treatment with EDTA appears to reverse most of the breaks (Figure 1, lanes 3, 5 and 7). This is reminiscent of the reversible topoisomerase II (Top2) - induced breaks that occur in somatic cells as the first step of DNA degradation during apoptosis.1117 Since Top2 is a nuclear matrix associated protein.71718 this first step of apoptotic DNA degradation occurs on the nuclear matrix, and results in the chromatin being digested to loop-sized fragments, about 50 kb in length. As apoptosis progresses, nucleases interact with Top2 to irreversibly continue the DNA degradation.1920 If SCF is allowed to progress further in epididymal sperm, a similar type of nonreversible degradation occurs.21 We also see this irreversible degradation in sperm cells as they progress through the reproductive tract. When vas deferens sperm are induced to undergo SCF, the degradation is more complete and cannot be reversed as completely (Figure 1, lanes 9, 11 and 13).

Bottom Line: The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization.This suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells.The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote.

View Article: PubMed Central - PubMed

Affiliation: Institute for Biogenesis Research, Department of Anatomy, Biochemistry and Physiology; Department of Obstetrics, Gynecology and Women's Health, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USA.

ABSTRACT
The highly condensed chromatin of mammalian spermatozoa is usually considered to be biologically inert before fertilization. However, we have demonstrated that even in this compacted state, sperm chromatin is subject to degradation at open configurations associated with the nuclear matrix through a process we have termed sperm chromatin fragmentation (SCF). This suggests that a mechanism exists to monitor the health of spermatozoa during transit through the male reproductive tract and to destroy the genome of defective sperm cells. The site of DNA damage in SCF, the matrix attachment sites, are the same that we hypothesize initiate DNA synthesis in the zygote. When sperm that have damaged DNA are injected into the oocyte, the newly created zygote responds by delaying DNA synthesis in the male pronucleus and, if the damage is severe enough, arresting the embryo's development. Here we present a model for paternal DNA regulation by the nuclear matrix that begins during sperm maturation and continues through early embryonic development.

No MeSH data available.


Related in: MedlinePlus