Heparan sulphate: a putative decondensing agent for human spermatozoa in vivo

Romanato, Marina; Cameo, Mónica S.; Bertolesi, Gabriel E.; Baldini, Consuelo; Calvo, Juan; Calvo, Lucrecia

doi:10.1093/humrep/deg354

Cited by 27 publications

(58 citation statements)

References 30 publications

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“…In human ICSI, it has been shown that the sperm DNA damage is detrimental to fertility and has been regarded as a major factor in lowering embryo quality (Tomsu et al 2002, Virant-Klun et al 2002, blastulation rate (Seli et al 2004), and overall pregnancy rate after IVF (Evenson et al 2002, Bungum et al 2004, Henkel et al 2004, Virro et al 2004. Heparin was also used to induce nuclear decondensation (Vendrell et al 1998, Delgado et al 2001, Romanato et al 2003. The glycoprotein heparin receptors are present on human sperm plasma membrane (Delgado et al 1982).…”

Section: Discussionmentioning

confidence: 99%

“…Binding of heparin to its receptors destabilizes sperm plasma membrane that in turn facilitates the incorporation of other molecules such as GSH into sperm nucleus (Marina et al 2003). Furthermore, the strong binding affinity of heparin for protamines can assist the formation of a highly insoluble complex that may promote sperm chromatin decondensation (reviewed in Romanato et al 2003). Combination of heparin and DTT may help to induce swelling of sperm nuclear matrix (Jager et al 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Other polyanions also can decondense sperm nuclei, but with lesser efficacy than heparin (Jager et al 1990). Romanato et al (2003) reported that the ability of heparin to decondense human sperm in vitro is related to its structural characteristics rather than its nature of being a polyanion. Whether heparin in combination with other disulphide bond reducing agents (i.e., GSH, DTT) enhances porcine sperm nuclear decondensation is presently unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of disulfide bond reducing agents on sperm chromatin structural integrity and developmental competence of in vitro matured oocytes after intracytoplasmic sperm injection in pigs

Cheng

An²,

Z³

et al. 2009

Reproduction

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We recently reported that electrical activation followed by secondary chemical activation greatly enhanced the developmental competence of in vitro matured porcine oocytes fertilized by intracytoplasmic sperm injection (ICSI). We hypothesized that sperm treatment with disulfide bond reducing agents will enhance the development competence of porcine embryos produced by this ICSI procedure. We examined the effects of glutathione (GSH), dithiothreitol (DTT), GSH or DTT in combination with heparin on sperm DNA structure, paternal chromosomal integrity, pronuclear formation, and developmental competence of in vitro matured porcine oocytes after ICSI. Acridine orange staining and flow cytometry based sperm chromatin structure assay were used to determine sperm DNA integrity by calculating the cells outside the main population (COMP aT). No differences were observed in COMP aT values among GSH-treated and control groups. COMP aT values in GSH-treated groups were significantly lower than that in DTT-treated groups. Following ICSI, GSH treatments did not significantly alter paternal chromosomal integrity. Paternal chromosomal integrity in sperm treated with DTT plus or minus heparin was also the lowest among all groups. GSH-treated sperm yielded the highest rates of normal fertilization and blastocyst formation, which were significantly higher than that of control and DTT-treated groups. The majority of blastocysts derived from control and GSH-treated spermatozoa were diploid, whereas blastocysts derived from DTT-treated spermatozoa were haploid. In conclusion, sperm treatment with GSH enhanced the developmental capacity of porcine embryos produced by our optimized ICSI procedure. Reproduction (2009) 137 633-643

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of disulfide bond reducing agents on sperm chromatin structural integrity and developmental competence of in vitro matured oocytes after intracytoplasmic sperm injection in pigs

Cheng

An²,

Z³

et al. 2009

Reproduction

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“…The procedure of sperm nuclear swelling using heparin and DTT mimics decondensation after fertilization, because both chemicals are analogs of components present in oocyte cytoplasm: disulfide-reducing glutathione (Sutovsky and Schatten, 1997) and heparan sulphate (Romanato et al, 2003). Care was taken to maintain the 3D structure of the nuclei using DNA-protein crosslinking by mild formaldehyde fixation.…”

Section: Discussionmentioning

confidence: 99%

Chromosome architecture in the decondensing human sperm nucleus

Mudrak

Tomilin

Zalensky

2005

Journal of Cell Science

103

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Whereas recent studies demonstrated a well-defined nuclear architecture in human sperm nuclei, little is known about the mode of DNA compaction above the elementary structural unit of nucleoprotamine toroids. Here, using fluorescence in-situ hybridization (FISH) with arm-specific DNA probes of chromosomes 1, 2 and 5, we visualized arm domains and established hierarchical levels of sperm chromatin structures. The compact chromosome territories, which in sperm have a preferred intranuclear localization, have an extended conformation represented by a 2000 nm chromatin fiber. This fiber is composed of a 1000 nm chromatin thread bent at 180° near centromere. Two threads of 1000 nm, representing p-arm and q-arm chromatin, run in antiparallel fashion and join at the telomeres. Each 1000 nm thread, in turn, resolves into two rows of chromatin globules 500 nm in diameter interconnected with thinner chromatin strands. We propose a unified comprehensive model of chromosomal and nuclear architecture in human sperm that, as we suggest, is important for successful fertilization and early development.

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“…The oocyte factors, known as sperm decondensation factors (SDFs), have been shown to induce this process (Moor & Gandolfi 1987, Miyara et al 2003. Several SDFs in oocytes that facilitate protamine removal, chromatin decondensation, and histone replacement have been identified to date (Romanato et al 2003, 2005, 2008, Inoue et al 2011, Julianelli et al 2012, Yadav et al 2013. It is suggested that SDFs are induced after GV breakdown in most mammals (Dozortsev et al 1995), but their roles and mechanisms of action in the oocyte cytoplasm are obscure at present.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of an oocyte factor required for sperm decondensation in pig

Xie

et al. 2014

Reproduction

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Mammalian oocytes possess factors to support fertilization and embryonic development, but knowledge on these oocyte-specific factors is limited. In the current study, we demonstrated that porcine oocytes with the first polar body collected at 33 h of in vitro maturation sustain IVF with higher sperm decondensation and pronuclear formation rates and support in vitro development with higher cleavage and blastocyst rates, compared with those collected at 42 h (P!0.05). Proteomic analysis performed to clarify the mechanisms underlying the differences in developmental competence between oocytes collected at 33 and 42 h led to the identification of 18 differentially expressed proteins, among which protein disulfide isomerase associated 3 (PDIA3) was selected for further study. Inhibition of maternal PDIA3 via antibody injection disrupted sperm decondensation; conversely, overexpression of PDIA3 in oocytes improved sperm decondensation. In addition, sperm decondensation failure in PDIA3 antibody-injected oocytes was rescued by dithiothreitol, a commonly used disulfide bond reducer. Our results collectively report that maternal PDIA3 plays a crucial role in sperm decondensation by reducing protamine disulfide bonds in porcine oocytes, supporting its utility as a potential tool for oocyte selection in assisted reproduction techniques.

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Heparan sulphate: a putative decondensing agent for human spermatozoa in vivo

Abstract: Our results indicate that heparin's decondensing ability in vitro is related to sulphation characteristics of the molecule and suggest that heparan sulphate, a structural analogue of heparin, could be a sperm-decondensing agent in vivo.

Cited by 27 publications

References 30 publications

Effects of disulfide bond reducing agents on sperm chromatin structural integrity and developmental competence of in vitro matured oocytes after intracytoplasmic sperm injection in pigs

Effects of disulfide bond reducing agents on sperm chromatin structural integrity and developmental competence of in vitro matured oocytes after intracytoplasmic sperm injection in pigs

Chromosome architecture in the decondensing human sperm nucleus

Identification and characterization of an oocyte factor required for sperm decondensation in pig

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