Dysplasia of the fibrous sheath: an ultrastructural defect of human spermatozoa associated with sperm immotility and primary sterility

Chemes, H; Brugo, S.; F, Zanchetti; Carrere, C.; Lavieri, J. C.

doi:10.1016/s0015-0282(16)59482-5

Cited by 157 publications

(126 citation statements)

References 13 publications

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“…Isolated ultrastructural defects are rare. Usually there will be a combination of multiple aberrations such as dysplasia of the fibrous sheath, dynein deficiency, and unassembled mitochondria at the mid-piece [37,38]. In one of the few papers to look at more than just one or a few patients; 247 severely asthenozoospermic patients where assessed for ultrastructural defects.…”

Section: Discussionmentioning

confidence: 99%

Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: A case report

Kordus

Price

Davis

et al. 2008

J Assist Reprod Genet

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Purpose To describe the ultrastructure of spermatozoa from a patient with complete asthenozoospermia that resulted in live births following blastocyst culture. Materials and methods Analyses of spermatozoa from a 36 year old patient were performed using light and electron microscopy. The hypo-osmotic swelling test was used to select spermatozoa for intracytoplasmic sperm injection. Embryos were cultured to the blastocyst stage. Results 100% of the spermatozoa had dynein arm deficiency with secondary defects varying from 3-17%. Six oocytes were injected; five fertilized normally and one was digynic. All five zygotes formed good quality blastocysts. Three blastocysts were cryopreserved and two blastocysts were transferred. Twin females were born at 37 weeks. Conclusions The hypo-osmotic swelling test can be used to select viable immotile ejaculated spermatozoa from a patient with dynein arm deficiency and can produce excellent fertilization rates and blastocyst development resulting in live births.

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Section: Discussionmentioning

confidence: 99%

Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: A case report

Kordus

Price

Davis

et al. 2008

J Assist Reprod Genet

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“…3,4 Men with MMAF have been previously reported as having dysplasia of fibrous sheath (DFS) and short tails. 5,6 The term MMAF was proposed in 2014 to provide a clear definition of the phenotypes in the affected individuals. 3 The incidence of MMAF or DFS has not been reported yet but was previously estimated to be higher than that of primary ciliary dyskinesia (PCD [MIM: 244400]; 1 per 10,000-20,000 births).…”

Section: Introductionmentioning

confidence: 99%

Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella

Tang¹,

Wang

Li³

et al. 2017

The American Journal of Human Genetics

242

212

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Sperm motility is vital to human reproduction. Malformations of sperm flagella can cause male infertility. Men with multiple morphological abnormalities of the flagella (MMAF) have abnormal spermatozoa with absent, short, coiled, bent, and/or irregular-caliber flagella, which impair sperm motility. The known human MMAF-associated genes, such as DNAH1, only account for fewer than 45% of affected individuals. Pathogenic mechanisms in the genetically unexplained MMAF remain to be elucidated. Here, we conducted genetic analyses by using whole-exome sequencing and genome-wide comparative genomic hybridization microarrays in a multi-center cohort of 30 Han Chinese men affected by MMAF. Among them, 12 subjects could not be genetically explained by any known MMAFassociated genes. Intriguingly, we identified compound-heterozygous mutations in CFAP43 in three subjects and a homozygous frameshift mutation in CFAP44 in one subject. All of these recessive mutations were parentally inherited from heterozygous carriers but were absent in 984 individuals from three Han Chinese control populations. CFAP43 and CFAP44, encoding two cilia-and flagella-associated proteins (CFAPs), are specifically or preferentially expressed in the testis. Using CRISPR/Cas9 technology, we generated two knockout models each deficient in mouse ortholog Cfap43 or Cfap44. Notably, both Cfap43-and Cfap44-deficient male mice presented with MMAF phenotypes, whereas the corresponding female mice were fertile. Our experimental observations on human subjects and animal models strongly suggest that biallelic mutations in either CFAP43 or CFAP44 can cause sperm flagellar abnormalities and impair sperm motility. Further investigations on other CFAP-encoding genes in more genetically unexplained MMAF-affected individuals could uncover novel mechanisms underlying sperm flagellar formation.

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“…Thioredoxins (Trx) 1 are low molecular weight proteins (12 kDa) that catalyze thiol-disulfide redox reactions by the reversible oxidation of the cysteine residues of their conserved active site WCGPC (1). Thioredoxins are maintained in their active reduced form by the flavoenzyme thioredoxin reductase that uses the reducing power of NADPH, which constitutes the so-called thioredoxin system (2).…”

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confidence: 99%

Characterization of Sptrx, a Novel Member of the Thioredoxin Family Specifically Expressed in Human Spermatozoa

Miranda‐Vizuete

Ljung

Damdimopoulos

et al. 2001

Journal of Biological Chemistry

138

125

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Thioredoxins (Trx) are small ubiquitous proteins that participate in different cellular processes via redox-mediated reactions. We report here the identification and characterization of a novel member of the thioredoxin family in humans, named Sptrx (sperm-specific trx), the first with a tissue-specific distribution, located exclusively in spermatozoa. Sptrx open reading frame encodes for a protein of 486 amino acids composed of two clear domains: an N-terminal domain consisting of 23 highly conserved repetitions of a 15-residue motif and a C-terminal domain typical of thioredoxins. Northern analysis and in situ hybridization shows that Sptrx mRNA is only expressed in human testis, specifically in round and elongating spermatids. Immunostaining of human testis sections identified Sptrx protein in spermatids, while immunofluorescence and immunogold electron microscopy analysis demonstrated Sptrx localization in the cytoplasmic droplet of ejaculated sperm. Sptrx appears to have a multimeric structure in native conditions and is able to reduce insulin disulfide bonds in the presence of NADPH and thioredoxin reductase. During mammalian spermiogenesis in testis seminiferous tubules and later maturation in epididymis, extensive reorganization of disulfide bonds is required to stabilize cytoskeletal sperm structures. However, the molecular mechanisms that control these processes are not known. The identification of Sptrx with an expression pattern restricted to the postmeiotic phase of spermatogenesis, when the sperm tail is organized, suggests that Sptrx might be an important factor in regulating critical steps of human spermiogenesis. Thioredoxins (Trx)1 are low molecular weight proteins (12 kDa) that catalyze thiol-disulfide redox reactions by the reversible oxidation of the cysteine residues of their conserved active site WCGPC (1). Thioredoxins are maintained in their active reduced form by the flavoenzyme thioredoxin reductase that uses the reducing power of NADPH, which constitutes the so-called thioredoxin system (2). All of the organisms from bacteria to humans appear to have at least one complete thioredoxin system, and the progressive complexity of eukaryotic organisms is also reflected in the increasing number of thioredoxin systems. Thus, Escherichia coli contains two thioredoxins and one thioredoxin reductase; yeast has two thioredoxin systems, one in cytosol and the other one in mitochondria; and photosynthetic organisms have several thioredoxin systems in different cellular compartments including chloroplasts. Finally, mammalian cells have at least two thioredoxin systems located in the cytosol and mitochondria, respectively (3). Different functions have been assigned to thioredoxins relying mostly on their general disulfide-reductase activity. In mammals, cytosolic Trx has been shown to be an antioxidant; a modulator of apoptosis, cell growth, and differentiation; and also a regulator of the DNA-binding activity of several transcription factors (following translocation into the nucleus), while the func...

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Dysplasia of the fibrous sheath: an ultrastructural defect of human spermatozoa associated with sperm immotility and primary sterility

Cited by 157 publications

References 13 publications

Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: A case report

Successful twin birth following blastocyst culture of embryos derived from the immotile ejaculated spermatozoa from a patient with primary ciliary dyskinesia: A case report

Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella

Characterization of Sptrx, a Novel Member of the Thioredoxin Family Specifically Expressed in Human Spermatozoa

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