Characterization of aneuploidy rates, protamine levels, ultrastructure, and functional ability of round-headed sperm from two siblings and implications for intracytoplasmic sperm injection

Carrell, Douglas T.; Emery, Benjamin R.; Liu, Lihua

doi:10.1016/s0015-0282(98)00498-1

Cited by 98 publications

(75 citation statements)

References 21 publications

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“…Indeed, some workers reported abnormal chromatin condensation in globozoospermia, with a high heterogeneity in the degree of maturity [33], due to an altered replacement of histones by protamines [34,35]. …”

Section: Meiotic Segregation Studies Several Workers Have Investigatementioning

confidence: 99%

“…The presence of consanguineous marriages in families affected with globozoospermia and reports of two or more sibs in several families suggested a genetic contribution to globozoospermia in humans with an autosomal recessive mode of inheritance [6,[35][36][37][38][39][40]. Three genes segregating on an autosomal recessive mode have now been identified to be associated with globozoospermia in humans.…”

Section: Molecular Genetic Studiesmentioning

confidence: 99%

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Genetic aspects of monomorphic teratozoospermia: a review

Braekeleer

Nguyen

Morel

et al. 2015

J Assist Reprod Genet

114

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Teratozoospermia is characterized by the presence of spermatozoa with abnormal morphology over 85 % in sperm. When all the spermatozoa display a unique abnormality, teratozoospermia is said to be monomorphic. Two forms of monomorphic teratozoospermia, representing less than 1 % of male infertility, are recognized: macrozoospermia (also called macrocephalic sperm head syndrome) and globozoospermia (also called round-headed sperm syndrome). Macrozoospermia is defined as the presence of a very high percentage of spermatozoa with enlarged head and multiple flagella. Meiotic segregation studies in 30 males revealed that over 90 % of spermatozoa were aneuploid, mainly diploid. Sperm DNA fragmentation studies performed in a few patients showed an increase in DNA fragmentation index compared to fertile men. Four mutations in the AURKC gene, a key player in meiosis and more particularly in spermatogenesis, have been found to be responsible for macrozoospermia. Globozoospermia is characterized by round-headed spermatozoa with an absent acrosome, an aberrant nuclear membrane and midpiece defects. The rate of aneuploidy of various chromosomes in spermatozoa from 26 globozoospermic men was slightly increased compared to fertile men. However, this increase was of the same order as that commonly found in infertile men with altered sperm parameters. The majority of the studies found that globozoospermic males had a sperm DNA fragmentation index higher than in fertile men. Mutations or deletions in three genes, SPATA16, PICK1 and DPY19L2, have been shown to be responsible for globozoospermia. Identification of the genetic causes of macrozoospermia and globozoospermia should help refine diagnosis and treatment of these patients, avoiding long and painful treatments. Elucidating the molecular causes of these defects is of utmost importance as intracytoplasmic sperm injection (ICSI) is very disappointing in these two pathologies.

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Section: Meiotic Segregation Studies Several Workers Have Investigatementioning

confidence: 99%

Section: Molecular Genetic Studiesmentioning

confidence: 99%

Genetic aspects of monomorphic teratozoospermia: a review

Braekeleer

Nguyen

Morel

et al. 2015

J Assist Reprod Genet

114

View full text Add to dashboard Cite

show abstract

“…Type II has some acrosomal activity covering a canonical nucleus surrounded by large cytoplasmic droplets [170]. Elevated chromosome aneuplodies were found in roundheaded sperms with FISH using probes for chromosomes 13,15,18,21, X, and Y [171,172], although this could not be confirmed by other authors [173,174]. However, in all cases an increased damage of the sperm chromatin structure has been reported, indicating a high mutational load in the paternal DNA structure of these patients.…”

Section: Male Infertility Syndromes With Poly-genic Inheritance Patternmentioning

confidence: 99%

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Vogt¹

2004

CPD

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Genetic lesions causing human male infertility are manifold. Besides gross chromosomal aneuploidies and rearrangements, microdeletions and single gene defects can interfere with male fertility. Male fertility is not only dependent on genes controlling the male germ line but also on genes of the networks functional for male gonad development and male somatic development, respectively. It is popular to unravel these netweorks with mouse gene knock-out mutants displaying reproductive defects. However, substantial arguments can be given for more functional studies directly on the human genes, because multiple reproductive proteins evolve quickly most likely for adopting to the specific needs of the species class. Prominent examples are mutations of the FSHR gene causing different pathologies in mouse and human and the DAZ gene family not found in the mouse genome but in the human genome with an essential male fertility function. Therefore this review is focussed on a comprehensive overview of human genes known with mutations causing male infertility (AR; AZF gene families; CFTR, DM-1, DNAH gene family, FGFR1, FSHR, INSL3, KAL-1, LGR8-GREAT, LHR, POLG). Then some human genes are described well recognised as functional in spermatogenesis and male fertility although gene specific mutations causing infertility were not yet identified (CREM, CDY1, DAZL1, PHGPx, PRM-1, PRM-2). They are designated as "spermatogenesis phase marker" or "male fertility index" genes, because they are useful tools for diagnosing the patient´s´ spermatogenesis disruption phase and for predicting the presence and quality of his mature sperms. Current therapeutic protocols for human male infertility do usually not cure the specific gene defect but try to bypass it using Artificial Reproductive Technology (ART). Putative imprinting defects in the early embryo probably associated with the used ART protocol and an increase of chromosome abnormalities in the ART offspring now strongly asks for a significant improvement of this outcome requesting urgently more basic research on the genes functioning in the human male germ line and during early human embryogenesis.

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“…It has previously been shown that generally these patients have lower sperm concentrations and motility than fertile men, and a higher frequency of abnormal sperm morphology and DNA damage than fertile controls. (14)(15)(16)(17)(19)(20)(21) Furthermore, lower pregnancy rates have also been reported in patients with abnormal protamine replacement, even when intracytoplasmic sperm injection is performed. 15,17,18,21 Whether aberrant protamination is the cause of infertility or simply an indication of other abnormalities during spermatogenesis is not known.…”

Section: Discussionmentioning

confidence: 99%

“…11,12,14,15 Several studies have reported that diminished sperm quality, increased DNA fragmentation and reduced pregnancy rates are associated with an altered protamine ratio. [14][15][16][17][18][19][20][21] However, the mechanism to explain how abnormal protamination results in altered semen quality and reduced pregnancy rates is not known.…”

Section: Introductionmentioning

confidence: 99%

Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination

Nánássy

Carrell²

2011

Asian J Androl

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It has recently been shown that alteration of the methylation pattern of imprinted genes is associated with different types of male infertility. The objective of our study was to investigate the methylation pattern of selected gene promoters in sperm of patients with abnormal protamine replacement. The promoters of OCT4, SOX2, NANOG, HOXC11, miR-17 and CREM were analyzed using bisulfite sequencing and the percentage of DNA methylation was compared between patients with an abnormal protamine 1/protamine 2 (P1/ P2) ratio and normozoospermic controls. No significant quantitative differences were found between groups of patients with either an abnormally high or low P1/P2 ratio compared to normal controls. However, two individual samples from infertile subjects (2/20, 10%) showed an altered methylation pattern for the CREM gene promoter that was not found in control samples. These two samples had a significantly higher (P,0.05) promoter methylation (5.58 and 4.23%, respectively) compared to the control group (0.46%). In conclusion, in our pilot study, extreme methylations defects were not seen broadly in severely infertile men. However, two patients exhibited altered methylation of the CREM gene, which may be either causative or a result of abnormal protmaine replacement.

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Characterization of aneuploidy rates, protamine levels, ultrastructure, and functional ability of round-headed sperm from two siblings and implications for intracytoplasmic sperm injection

Cited by 98 publications

References 21 publications

Genetic aspects of monomorphic teratozoospermia: a review

Genetic aspects of monomorphic teratozoospermia: a review

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Analysis of the methylation pattern of six gene promoters in sperm of men with abnormal protamination

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